Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease

Alan Chait1, Laura J. den Hartigh1
1Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, United States

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Flegal, 2012, Prevalence of obesity and trends in the distribution of body mass index among us adults, 1999-2010, JAMA, 307, 491, 10.1001/jama.2012.39

Abdullah, 2010, The magnitude of association between overweight and obesity and the risk of diabetes: a meta-analysis of prospective cohort studies, Diabetes Res Clin Pract, 89, 309, 10.1016/j.diabres.2010.04.012

Flegal, 1998, Overweight and obesity in the United States: prevalence and trends, 1960-1994, Int J Obes Relat Metab Disord, 22, 39, 10.1038/sj.ijo.0800541

2004, Prevalence of overweight and obesity among adults with diagnosed diabetes–United States, 1988-1994 and 1999-2002, MMWR Morb Mortal Wkly Rep, 53, 1066

2016, Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants, Lancet, 387, 1513, 10.1016/S0140-6736(16)00618-8

Defronzo, 2009, Banting lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus, Diabetes, 58, 773, 10.2337/db09-9028

Rao Kondapally Seshasai, 2011, Diabetes mellitus, fasting glucose, and risk of cause-specific death, N Engl J Med, 364, 829, 10.1056/NEJMoa1008862

Lloyd-Jones, 2010, Defining and setting national goals for cardiovascular health promotion and disease reduction: the American heart association's strategic impact goal through 2020 and beyond, Circulation, 121, 586, 10.1161/CIRCULATIONAHA.109.192703

Cornier, 2011, Assessing adiposity: a scientific statement from the American heart association, Circulation, 124, 1996, 10.1161/CIR.0b013e318233bc6a

Flint, 2010, Excess weight and the risk of incident coronary heart disease among men and women, Obesity, 18, 377, 10.1038/oby.2009.223

Lee, 2008, Indices of abdominal obesity are better discriminators of cardiovascular risk factors than bmi: a meta-analysis, J Clin Epidemiol, 61, 646, 10.1016/j.jclinepi.2007.08.012

Chusyd, 2016, Relationships between rodent white adipose fat pads and human white adipose fat depots, Front Nutr, 3, 10, 10.3389/fnut.2016.00010

Reddy, 2019, Metabolic syndrome is an inflammatory disorder: a conspiracy between adipose tissue and phagocytes, Clin Chim Acta, 496, 35, 10.1016/j.cca.2019.06.019

Freedl, 2004, Role of a critical visceral adipose tissue threshold (cvatt) in metabolic syndrome: implications for controlling dietary carbohydrates: a review, Nutr Metab., 1, 12, 10.1186/1743-7075-1-12

Kwok, 2016, Heterogeneity of white adipose tissue: molecular basis and clinical implications, Exp Mol Med, 48, e215, 10.1038/emm.2016.5

Gesta, 2006, Evidence for a role of developmental genes in the origin of obesity and body fat distribution, Proc Natl Acad Sci USA, 103, 6676, 10.1073/pnas.0601752103

Baker, 2005, Association between common polymorphisms of the proopiomelanocortin gene and body fat distribution: a family study, Diabetes, 54, 2492, 10.2337/diabetes.54.8.2492

Ho, 1978, Formation of the epicardium studied with the scanning electron microscope, Dev Biol, 66, 579, 10.1016/0012-1606(78)90263-4

Iacobellis, 2005, Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart, Nat Clin Pract Cardiovasc Med, 2, 536, 10.1038/ncpcardio0319

Marchington, 1989, Adipose tissue in the mammalian heart and pericardium: structure, foetal development and biochemical properties, Comp Biochem Physiol B, 94, 225, 10.1016/0305-0491(89)90337-4

Mazurek, 2003, Human epicardial adipose tissue is a source of inflammatory mediators, Circulation, 108, 2460, 10.1161/01.CIR.0000099542.57313.C5

Iacobellis, 2011, Epicardial fat: from the biomolecular aspects to the clinical practice, Int J Biochem Cell Biol, 43, 1651, 10.1016/j.biocel.2011.09.006

Szasz, 2012, Perivascular adipose tissue: more than just structural support, Clin Sci, 122, 1, 10.1042/CS20110151

Qi, 2018, Perivascular adipose tissue (pvat) in atherosclerosis: a double-edged sword, Cardiovasc Diabetol, 17, 134, 10.1186/s12933-018-0777-x

Björntorp, 1990, Portal Adipose tissue as a generator of risk factors for cardiovascular disease and diabetes, Arteriosclerosis, 10, 493, 10.1161/01.ATV.10.4.493

Zhang, 2018, An adipose tissue atlas: an image-guided identification of human-like bat and beige depots in rodents, Cell Metab, 27, 252, 10.1016/j.cmet.2017.12.004

Cannon, 2004, Brown adipose tissue: function and physiological significance, Physiol Rev, 84, 277, 10.1152/physrev.00015.2003

Cypess, 2009, Identification and importance of brown adipose tissue in adult humans, N Engl J Med, 360, 1509, 10.1056/NEJMoa0810780

Cypess, 2015, Activation of human brown adipose tissue by a β3-adrenergic receptor agonist, Cell Metab, 21, 33, 10.1016/j.cmet.2014.12.009

Cypess, 2013, Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat, Nat Med, 19, 635, 10.1038/nm.3112

Kahn, 2019, Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome, J Clin Invest, 129, 3990, 10.1172/JCI129187

Hany, 2002, Brown adipose tissue: a factor to consider in symmetrical tracer uptake in the neck and upper chest region, Eur J Nucl Med Mol Imaging, 29, 1393, 10.1007/s00259-002-0902-6

Lee, 2019, Adipose tissue-derived signatures for obesity and type 2 diabetes: adipokines, batokines and micrornas, J Clin Med, 8, E854, 10.3390/jcm8060854

Srivastava, 2019, Brown and brite: the fat soldiers in the anti-obesity fight, Front Physiol, 10, 38, 10.3389/fphys.2019.00038

Waldén, 2012, Recruited vs. Nonrecruited molecular signatures of brown, Brite, and white adipose tissues, Am J Physiol Endocrinol Metab, 302, E19, 10.1152/ajpendo.00249.2011

Wu, 2012, Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human, Cell, 150, 366, 10.1016/j.cell.2012.05.016

Jespersen, 2013, A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans, Cell Metab, 17, 798, 10.1016/j.cmet.2013.04.011

Sharp, 2012, Human bat possesses molecular signatures that resemble beige/brite cells, PLoS ONE, 7, e49452, 10.1371/journal.pone.0049452

Shinoda, 2015, Genetic and functional characterization of clonally derived adult human brown adipocytes, Nat Med, 21, 389, 10.1038/nm.3819

Zuriaga, 2017, Humans and mice display opposing patterns of Browning Gene expression in visceral and subcutaneous white adipose tissue depots, Front Cardiovasc Med, 4, 27, 10.3389/fcvm.2017.00027

Kir, 2014, Tumour-derived pth-related protein triggers adipose tissue browning and cancer cachexia, Nature, 513, 100, 10.1038/nature13528

Neinast, 2015, Activation of natriuretic peptides and the sympathetic nervous system following roux-en-y gastric bypass is associated with gonadal adipose tissues browning, Mol Metab, 4, 427, 10.1016/j.molmet.2015.02.006

Sidossis, 2015, Browning of subcutaneous white adipose tissue in humans after severe adrenergic stress, Cell Metab, 22, 219, 10.1016/j.cmet.2015.06.022

den Hartigh, 2017, Metabolically distinct weight loss by 10,12 cla and caloric restriction highlight the importance of subcutaneous white adipose tissue for glucose homeostasis in mice, PLoS ONE, 12, e0172912, 10.1371/journal.pone.0172912

Sahuri-Arisoylu, 2016, Reprogramming of hepatic fat accumulation and 'browning' of adipose tissue by the short-chain fatty acid acetate, Int J Obes, 40, 955, 10.1038/ijo.2016.23

Ghorbani, 1997, Appearance of brown adipocytes in white adipose tissue during cl 316,243-induced reversal of obesity and diabetes in zucker fa/fa rats, Int J Obes Relat Metab Disord, 21, 465, 10.1038/sj.ijo.0800432

Baskaran, 2016, Capsaicin induces browning of white adipose tissue and counters obesity by activating trpv1 channel-dependent mechanisms, Br J Pharmacol, 173, 2369, 10.1111/bph.13514

Chen, 2017, Green tea extract induces genes related to browning of white adipose tissue and limits weight-gain in high energy diet-fed rat, Food Nutr Res, 61, 1347480, 10.1080/16546628.2017.1347480

Petrovic, 2010, Chronic peroxisome proliferator-activated receptor gamma (ppargamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, ucp1-containing adipocytes molecularly distinct from classic brown adipocytes, J Biol Chem, 285, 7153, 10.1074/jbc.M109.053942

Lin, 2012, Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms, PLoS ONE, 7, e35240, 10.1371/journal.pone.0035240

Fukui, 2000, A new thiazolidinedione, nc-2100, which is a weak ppar-gamma activator, exhibits potent antidiabetic effects and induces uncoupling protein 1 in white adipose tissue of kkay obese mice, Diabetes, 49, 759, 10.2337/diabetes.49.5.759

Stanford, 2015, Exercise effects on white adipose tissue: beiging and metabolic adaptations, Diabetes, 64, 2361, 10.2337/db15-0227

Seale, 2008, Prdm16 controls a brown fat/skeletal muscle switch, Nature, 454, 961, 10.1038/nature07182

Shao, 2019, Cellular origins of beige fat cells revisited, Diabetes, 68, 1874, 10.2337/db19-0308

Barbatelli, 2010, The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation, Am J Physiol Endocrinol Metab, 298, E1244, 10.1152/ajpendo.00600.2009

Cinti, 2009, Transdifferentiation properties of adipocytes in the adipose organ, Am J Physiol Endocrinol Metab, 297, E977, 10.1152/ajpendo.00183.2009

Altshuler-Keylin, 2016, Beige adipocyte maintenance is regulated by autophagy-induced mitochondrial clearance, Cell Metab, 24, 402, 10.1016/j.cmet.2016.08.002

Xue, 2015, Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes, Nat Med, 21, 760, 10.1038/nm.3881

Guerra, 1998, Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity, J Clin Invest, 102, 412, 10.1172/JCI3155

Almind, 2004, Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice, Diabetes, 53, 3274, 10.2337/diabetes.53.12.3274

Collins, 1997, Strain-specific response to beta 3-adrenergic receptor agonist treatment of diet-induced obesity in mice, Endocrinology, 138, 405, 10.1210/endo.138.1.4829

Seale, 2011, Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice, J Clin Invest, 121, 96, 10.1172/JCI44271

Shao, 2016, Zfp423 maintains white adipocyte identity through suppression of the beige cell thermogenic gene program, Cell Metab, 23, 1167, 10.1016/j.cmet.2016.04.023

Qatanani, 2007, Mechanisms of obesity-associated insulin resistance: many choices on the menu, Genes Dev, 21, 1443, 10.1101/gad.1550907

Schoettl, 2018, Heterogeneity of adipose tissue in development and metabolic function, J Exp Biol, 221, jeb162958, 10.1242/jeb.162958

Chondronikola, 2016, Brown adipose tissue is linked to a distinct thermoregulatory response to mild cold in people, Front Physiol, 7, 129, 10.3389/fphys.2016.00129

Frontini, 2010, Distribution and development of brown adipocytes in the murine and human adipose organ, Cell Metab, 11, 253, 10.1016/j.cmet.2010.03.004

Yoneshiro, 2013, Recruited brown adipose tissue as an antiobesity agent in humans, J Clin Invest, 123, 3404, 10.1172/JCI67803

Harms, 2013, Brown and beige fat: development, function and therapeutic potential, Nat Med, 19, 1252, 10.1038/nm.3361

Nguyen, 2011, Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis, Nature, 480, 104, 10.1038/nature10653

Qiu, 2014, Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat, Cell, 157, 1292, 10.1016/j.cell.2014.03.066

Shan, 2017, The metabolic er stress sensor ire1α suppresses alternative activation of macrophages and impairs energy expenditure in obesity, Nat Immunol, 18, 519, 10.1038/ni.3709

Vargovic, 2016, Continuous cold exposure induces an anti-inflammatory response in mesenteric adipose tissue associated with catecholamine production and thermogenin expression in rats, Endocr Regul, 50, 137, 10.1515/enr-2016-0015

Liu, 2015, Injecting engineered anti-inflammatory macrophages therapeutically induces white adipose tissue browning and improves diet-induced insulin resistance, Adipocyte, 4, 123, 10.4161/21623945.2014.981438

Liu, 2014, Reducing rip140 expression in macrophage alters atm infiltration, facilitates white adipose tissue browning, and prevents high-fat diet-induced insulin resistance, Diabetes, 63, 4021, 10.2337/db14-0619

Kusminski, 2012, Mitoneet-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity, Nat Med, 18, 1539, 10.1038/nm.2899

Hallowell, 2017, Mtorc2 signalling regulates m2 macrophage differentiation in response to helminth infection and adaptive thermogenesis, Nat Commun, 8, 14208, 10.1038/ncomms14208

Brestoff, 2015, Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity, Nature, 519, 242, 10.1038/nature14115

Lee, 2015, Activated type 2 innate lymphoid cells regulate beige fat biogenesis, Cell, 160, 74, 10.1016/j.cell.2014.12.011

Fischer, 2017, Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis, Nat Med, 23, 623, 10.1038/nm.4316

Ahima, 2008, Adipokines and the peripheral and neural control of energy balance, Mol Endocrinol, 22, 1023, 10.1210/me.2007-0529

Friedman, 2016, The long road to leptin, J Clin Invest, 126, 4727, 10.1172/JCI91578

Farooqi, 2014, 20 years of leptin: human disorders of leptin action, J Endocrinol, 223, T63, 10.1530/JOE-14-0480

Considine, 1996, Serum immunoreactive-leptin concentrations in normal-weight and obese humans, N Engl J Med, 334, 292, 10.1056/NEJM199602013340503

Boden, 1996, Effect of fasting on serum leptin in normal human subjects, J Clin Endocrinol Metab, 81, 3419, 10.1210/jcem.81.9.8784108

Hube, 1996, Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans, Horm Metab Res, 28, 690, 10.1055/s-2007-979879

Hu, 1996, Adipoq is a novel adipose-specific gene dysregulated in obesity, J Biol Chem, 271, 10697, 10.1074/jbc.271.18.10697

Maeda, 1996, Cdna cloning and expression of a novel adipose specific collagen-like factor, apm1 (adipose most abundant gene transcript 1), Biochem Biophys Res Commun, 221, 286, 10.1006/bbrc.1996.0587

Nakano, 1996, Isolation and characterization of gbp28, a novel gelatin-binding protein purified from human plasma, J Biochem, 120, 803, 10.1093/oxfordjournals.jbchem.a021483

Scherer, 1995, A novel serum protein similar to c1q, produced exclusively in adipocytes, J Biol Chem, 270, 26746, 10.1074/jbc.270.45.26746

Cnop, 2003, Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex, Diabetologia, 46, 459, 10.1007/s00125-003-1074-z

Kern, 2003, Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression, Diabetes, 52, 1779, 10.2337/diabetes.52.7.1779

Kishida, 2011, Relationships between circulating adiponectin levels and fat distribution in obese subjects, J Atheroscler Thromb, 18, 592, 10.5551/jat.7625

Samaras, 2010, Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes, Obesity, 18, 884, 10.1038/oby.2009.443

Lihn, 2004, Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects, Mol Cell Endocrinol, 219, 9, 10.1016/j.mce.2004.03.002

Maeda, 2002, Diet-induced insulin resistance in mice lacking adiponectin/acrp30, Nat Med, 8, 731, 10.1038/nm724

Kim, 2007, Obesity-associated improvements in metabolic profile through expansion of adipose tissue, J Clin Invest, 117, 2621, 10.1172/JCI31021

Yamauchi, 2003, cloning of adiponectin receptors that mediate antidiabetic metabolic effects, Nature, 423, 762, 10.1038/nature01705

Fang, 2018, Adiponectin regulation and function, Compr Physiol, 8, 1031, 10.1002/cphy.c170046

Ye, 2015, Adiponectin-mediated antilipotoxic effects in regenerating pancreatic islets, Endocrinology, 156, 2019, 10.1210/en.2015-1066

Mandal, 2011, Molecular mechanism for adiponectin-dependent m2 macrophage polarization: link between the metabolic and innate immune activity of full-length adiponectin, J Biol Chem, 286, 13460, 10.1074/jbc.M110.204644

Caligiuri, 2008, Adenosine monophosphate-activated protein kinase modulates the activated phenotype of hepatic stellate cells, Hepatology, 47, 668, 10.1002/hep.21995

Jamaluddin, 2012, Resistin: functional roles and therapeutic considerations for cardiovascular disease, Br J Pharmacol, 165, 622, 10.1111/j.1476-5381.2011.01369.x

Savage, 2001, Resistin / fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans, Diabetes, 50, 2199, 10.2337/diabetes.50.10.2199

Tsiotra, 2008, Peripheral mononuclear cell resistin mRNA expression is increased in type 2 diabetic women, Mediators Inflamm, 2008, 892864, 10.1155/2008/892864

Ghosh, 2003, The genomic organization of mouse resistin reveals major differences from the human resistin: functional implications, Gene, 305, 27, 10.1016/S0378-1119(02)01213-1

Park, 2013, Resistin in rodents and humans, Diabetes Metab J, 37, 404, 10.4093/dmj.2013.37.6.404

Steppan, 2001, The hormone resistin links obesity to diabetes, Nature, 409, 307, 10.1038/35053000

Sheng, 2008, Resistin is expressed in human hepatocytes and induces insulin resistance, Endocrine, 33, 135, 10.1007/s12020-008-9065-y

Yannakoulia, 2003, Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans, J Clin Endocrinol Metab, 88, 1730, 10.1210/jc.2002-021604

Degawa-Yamauchi, 2003, Serum resistin (fizz3) protein is increased in obese humans, J Clin Endocrinol Metab, 88, 5452, 10.1210/jc.2002-021808

McTernan, 2002, Resistin, central obesity, and type 2 diabetes, Lancet, 359, 46, 10.1016/S0140-6736(02)07281-1

McTernan, 2002, Increased resistin gene and protein expression in human abdominal adipose tissue, J Clin Endocrinol Metab, 87, 2407, 10.1210/jcem.87.5.8627

Valsamakis, 2004, Modest weight loss and reduction in waist circumference after medical treatment are associated with favorable changes in serum adipocytokines, Metabolism, 53, 430, 10.1016/j.metabol.2003.11.022

Way, 2001, Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists, J Biol Chem, 276, 25651, 10.1074/jbc.C100189200

Janke, 2002, Resistin gene expression in human adipocytes is not related to insulin resistance, Obes Res, 10, 1, 10.1038/oby.2002.1

Vidal-Puig, 2001, Resistin: a new link between obesity and insulin resistance?, Clin Endocrinol, 55, 437, 10.1046/j.1365-2265.2001.01377.x

Bokarewa, 2005, Resistin, an adipokine with potent proinflammatory properties, J Immunol, 174, 5789, 10.4049/jimmunol.174.9.5789

Yang, 2006, Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action, Am J Physiol Endocrinol Metab, 290, E1253, 10.1152/ajpendo.00572.2004

Landecho, 2019, Relevance of leptin and other adipokines in obesity-associated cardiovascular risk, Nutrients, 11, 2664, 10.3390/nu11112664

Schäffler, 2005, Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue, Biochim Biophys Acta, 1732, 96, 10.1016/j.bbaexp.2005.11.005

Auguet, 2011, New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women, BMC Med Genet, 12, 60, 10.1186/1471-2350-12-60

de Souza Batista, 2007, Omentin plasma levels and gene expression are decreased in obesity, Diabetes, 56, 1655, 10.2337/db06-1506

Pan, 2010, Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes, Diabetes Res Clin Pract, 88, 29, 10.1016/j.diabres.2010.01.013

Tan, 2008, Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome: ex vivo and in vivo regulation of omentin-1 by insulin and glucose, Diabetes, 57, 801, 10.2337/db07-0990

Cai, 2009, [Expression of omentin in adipose tissues in obese and type 2 diabetic patients], Zhonghua Yi Xue Za Zhi, 89, 381

Elsaid, 2018, Serum omentin-1 levels in type 2 diabetic obese women in relation to glycemic control, insulin resistance and metabolic parameters, J Clin Transl Endocrinol, 13, 14, 10.1016/j.jcte.2018.05.003

Zhang, 2017, Serum levels of omentin-1 are increased after weight loss and are particularly associated with increases in obese children with metabolic syndrome, Acta Paediatr, 106, 1851, 10.1111/apa.14026

Moreno-Navarrete, 2010, Circulating omentin concentration increases after weight loss, Nutr Metab, 7, 27, 10.1186/1743-7075-7-27

Yamawaki, 2011, Omentin, a novel adipocytokine inhibits tnf-induced vascular inflammation in human endothelial cells, Biochem Biophys Res Commun, 408, 339, 10.1016/j.bbrc.2011.04.039

Kazama, 2012, Omentin plays an anti-inflammatory role through inhibition of TNF-α-induced superoxide production in vascular smooth muscle cells, Eur J Pharmacol, 686, 116, 10.1016/j.ejphar.2012.04.033

Kazama, 2014, A novel adipocytokine, omentin, inhibits platelet-derived growth factor-bb-induced vascular smooth muscle cell migration through antioxidative mechanism, Am J Physiol Heart Circ Physiol, 306, H1714, 10.1152/ajpheart.00048.2014

Wang, 2019, Omentin-1 attenuates lipopolysaccharide (LPS)-induced U937 macrophages activation by inhibiting the TLR4/MyD88/NF-κB signaling, Arch Biochem Biophys, 679, 108187, 10.1016/j.abb.2019.108187

Kazama, 2015, Adipocytokine, omentin inhibits doxorubicin-induced h9c2 cardiomyoblasts apoptosis through the inhibition of mitochondrial reactive oxygen species, Biochem Biophys Res Commun, 457, 602, 10.1016/j.bbrc.2015.01.032

Fernández-Trasancos, 2017, Omentin treatment of epicardial fat improves its anti-inflammatory activity and paracrine benefit on smooth muscle cells, Obesity, 25, 1042, 10.1002/oby.21832

Zabetian-Targhi, 2016, Modulatory role of omentin-1 in inflammation: cytokines and dietary intake, J Am Coll Nutr, 35, 670, 10.1080/07315724.2015.1126207

Shibata, 2012, Omentin as a novel biomarker of metabolic risk factors, Diabetol Metab Syndr, 4, 37, 10.1186/1758-5996-4-37

Cuevas-Ramos, 2009, The role of fibroblast growth factor 21 (fgf21) on energy balance, glucose and lipid metabolism, Curr Diabetes Rev, 5, 216, 10.2174/157339909789804396

Coskun, 2008, Fibroblast growth factor 21 corrects obesity in mice, Endocrinology, 149, 6018, 10.1210/en.2008-0816

Markan, 2014, Circulating fgf21 is liver derived and enhances glucose uptake during refeeding and overfeeding, Diabetes, 63, 4057, 10.2337/db14-0595

BonDurant, 2017, Fgf21 regulates metabolism through adipose-dependent and -independent mechanisms, Cell Metab, 25, 935, 10.1016/j.cmet.2017.03.005

Talukdar, 2016, A long-acting fgf21 molecule, pf-05231023, decreases body weight and improves lipid profile in non-human primates and type 2 diabetic subjects, Cell Metab, 23, 427, 10.1016/j.cmet.2016.02.001

Izumiya, 2008, fgf21 is an akt-regulated myokine, FEBS Lett, 582, 3805, 10.1016/j.febslet.2008.10.021

Lin, 2017, metabolic role of fibroblast growth factor 21 in liver, adipose and nervous system tissues, Biomed Rep, 6, 495, 10.3892/br.2017.890

Zhang, 2008, Serum fgf21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans, Diabetes, 57, 1246, 10.2337/db07-1476

Fisher, 2010, Obesity is a fibroblast growth factor 21 (fgf21)-resistant state, Diabetes, 59, 2781, 10.2337/db10-0193

Crujeiras, 2017, Plasma fgf21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: a marker of metabolic stress?, Int J Obes, 41, 1570, 10.1038/ijo.2017.138

Berti, 2015, Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes, Mol Metab, 4, 519, 10.1016/j.molmet.2015.04.002

Mashili, 2018, Adiposity is a key correlate of circulating fibroblast growth factor-21 levels in African males with or without type 2 diabetes mellitus, J Obes, 2018, 7461903, 10.1155/2018/7461903

Sandoval, 2018, Mediterranean tomato-based sofrito sauce improves fibroblast growth factor 21 (fgf21) signaling in white adipose tissue of obese zucker rats, Mol Nutr Food Res, 62, 1, 10.1002/mnfr.201700606

Fon Tacer, 2010, Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse, Mol Endocrinol, 24, 2050, 10.1210/me.2010-0142

Muise, 2008, Adipose fibroblast growth factor 21 is up-regulated by peroxisome proliferator-activated receptor gamma and altered metabolic states, Mol Pharmacol, 74, 403, 10.1124/mol.108.044826

Miehle, 2016, Serum concentrations of fibroblast growth factor 21 are elevated in patients with congenital or acquired lipodystrophy, Cytokine, 83, 239, 10.1016/j.cyto.2016.04.015

Keipert, 2015, Genetic disruption of uncoupling protein 1 in mice renders brown adipose tissue a significant source of fgf21 secretion, Mol Metab, 4, 537, 10.1016/j.molmet.2015.04.006

Gerhard, 2014, Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity, Int J Obes, 38, 371, 10.1038/ijo.2013.152

van Baak, 2019, Adipose tissue contribution to plasma fibroblast growth factor 21 and fibroblast activation protein in obesity, Int J Obes, 44, 544, 10.1038/s41366-019-0433-x

Hong, 2019, Plasma fibroblast growth factor 21 levels increase with ectopic fat accumulation and its receptor levels are decreased in the visceral fat of patients with type 2 diabetes, BMJ Open Diabetes Res Care, 7, e000776, 10.1136/bmjdrc-2019-000776

Mraz, 2009, Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity, Clin Endocrinol, 71, 369, 10.1111/j.1365-2265.2008.03502.x

Kotulák, 2011, Increased circulating and epicardial adipose tissue mRNA expression of fibroblast growth factor-21 after cardiac surgery: possible role in postoperative inflammatory response and insulin resistance, Physiol Res, 60, 757, 10.33549/physiolres.932134

Lee, 2018, Clinical implications of ucp1 mRNA expression in human cervical adipose tissue under physiological conditions, Obesity, 26, 1008, 10.1002/oby.22188

Lee, 2014, Functional thermogenic beige adipogenesis is inducible in human neck fat, Int J Obes, 38, 170, 10.1038/ijo.2013.82

Vargas, 2018, Thermogenic capacity of human periaortic adipose tissue is transformed by body weight, PLoS ONE, 13, e0194269, 10.1371/journal.pone.0194269

Vargas, 2017, Functional characterization of preadipocytes derived from human periaortic adipose tissue, Int J Endocrinol, 2017, 2945012, 10.1155/2017/2945012

Cuevas-Ramos, 2010, Daily physical activity, fasting glucose, uric acid, and body mass index are independent factors associated with serum fibroblast growth factor 21 levels, Eur J Endocrinol, 163, 469, 10.1530/EJE-10-0454

Gómez-Sámano, 2017, Fibroblast growth factor 21 and its novel association with oxidative stress, Redox Biol, 11, 335, 10.1016/j.redox.2016.12.024

Hondares, 2011, Thermogenic activation induces fgf21 expression and release in brown adipose tissue, J Biol Chem, 286, 12983, 10.1074/jbc.M110.215889

Spalding, 2008, Dynamics of fat cell turnover in humans, Nature, 453, 783, 10.1038/nature06902

Goossens, 2015, Adipose tissue dysfunction and impaired metabolic health in human obesity: a matter of oxygen?, Front Endocrinol, 6, 55, 10.3389/fendo.2015.00055

Wang, 2014, The adipochaser mouse: a model tracking adipogenesis in vivo, Adipocyte, 3, 146, 10.4161/adip.27656

Wang, 2013, Tracking adipogenesis during white adipose tissue development, expansion and regeneration, Nat Med, 19, 1338, 10.1038/nm.3324

Kim, 2014, Loss of white adipose hyperplastic potential is associated with enhanced susceptibility to insulin resistance, Cell Metab, 20, 1049, 10.1016/j.cmet.2014.10.010

Guillermier, 2017, Imaging mass spectrometry demonstrates age-related decline in human adipose plasticity, JCI Insight, 2, e90349, 10.1172/jci.insight.90349

Denis, 2013, ‘Metabolically healthy obesity': origins and implications, Mol Aspects Med, 34, 59, 10.1016/j.mam.2012.10.004

Stefan, 2013, Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications, Lancet Diabetes Endocrinol, 1, 152, 10.1016/S2213-8587(13)70062-7

Samocha-Bonet, 2014, Metabolically healthy and unhealthy obese–the 2013 stock conference report, Obes Rev, 15, 697, 10.1111/obr.12199

Smith, 2019, Metabolically healthy obesity: facts and fantasies, J Clin Invest, 129, 3978, 10.1172/JCI129186

Naukkarinen, 2014, Characterising metabolically healthy obesity in weight-discordant monozygotic twins, Diabetologia, 57, 167, 10.1007/s00125-013-3066-y

Rey-López, 2014, The prevalence of metabolically healthy obesity: a systematic review and critical evaluation of the definitions used, Obes Rev, 15, 781, 10.1111/obr.12198

Karelis, 2005, The metabolically healthy but obese individual presents a favorable inflammation profile, J Clin Endocrinol Metab, 90, 4145, 10.1210/jc.2005-0482

Blüher, 2010, The distinction of metabolically ‘healthy' from ‘unhealthy' obese individuals, Curr Opin Lipidol, 21, 38, 10.1097/MOL.0b013e3283346ccc

Echouffo-Tcheugui, 2019, Natural history of obesity subphenotypes: dynamic changes over two decades and prognosis in the framingham heart study, J Clin Endocrinol Metab, 104, 738, 10.1210/jc.2018-01321

Mongraw-Chaffin, 2018, Metabolically healthy obesity, transition to metabolic syndrome, and cardiovascular risk, J Am Coll Cardiol, 71, 1857, 10.1016/j.jacc.2018.02.055

Soriguer, 2013, Metabolically healthy but obese, a matter of time? Findings from the prospective pizarra study, J Clin Endocrinol Metab, 98, 2318, 10.1210/jc.2012-4253

Kouvari, 2019, Transition from metabolically benign to metabolically unhealthy obesity and 10-year cardiovascular disease incidence: the attica cohort study, Metabolism, 93, 18, 10.1016/j.metabol.2019.01.003

Caleyachetty, 2017, Metabolically healthy obese and incident cardiovascular disease events among 3.5 million men and women, J Am Coll Cardiol, 70, 1429, 10.1016/j.jacc.2017.07.763

Twig, 2014, Diabetes risk among overweight and obese metabolically healthy young adults, Diabetes Care, 37, 2989, 10.2337/dc14-0869

Guo, 2014, The progression of cardiometabolic disease: validation of a new cardiometabolic disease staging system applicable to obesity, Obesity, 22, 110, 10.1002/oby.20585

Johnson, 2019, Do worse baseline risk factors explain the association of healthy obesity with increased mortality risk? Whitehall II study, Int J Obes, 43, 1578, 10.1038/s41366-018-0192-0

Shin, 2006, Weight loss effect on inflammation and ldl oxidation in metabolically healthy but obese (mho) individuals: low inflammation and ldl oxidation in mho women, Int J Obes, 30, 1529, 10.1038/sj.ijo.0803304

Karelis, 2008, Metabolically healthy but obese women: effect of an energy-restricted diet, Diabetologia, 51, 1752, 10.1007/s00125-008-1038-4

Kantartzis, 2011, Effects of a lifestyle intervention in metabolically benign and malign obesity, Diabetologia, 54, 864, 10.1007/s00125-010-2006-3

Blüher, 2014, Are metabolically healthy obese individuals really healthy?, Eur J Endocrinol, 171, R209, 10.1530/EJE-14-0540

Yang, 2007, Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer?, Diabetologia, 50, 1127, 10.1007/s00125-007-0640-1

Yki-Järvinen, 2014, Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome, Lancet Diabetes Endocrinol, 2, 901, 10.1016/S2213-8587(14)70032-4

Ruderman, 1981, The Metabolically-Obese, Normal-weight individual, Am J Clin Nutr, 34, 1617, 10.1093/ajcn/34.8.1617

Newell-Morris, 1989, Fatness, fat distribution, and glucose tolerance in second-generation Japanese-American (nisei) men, Am J Clin Nutr, 50, 9, 10.1093/ajcn/50.1.9

Jensen, 2006, Is visceral fat involved in the pathogenesis of the metabolic syndrome? Human model, Obesity, 14, 20S, 10.1038/oby.2006.278

Karpe, 2015, Biology of upper-body and lower-body adipose tissue–link to whole-body phenotypes, Nat Rev Endocrinol, 11, 90, 10.1038/nrendo.2014.185

Vega, 2006, Influence of body fat content and distribution on variation in metabolic risk, J Clin Endocrinol Metab, 91, 4459, 10.1210/jc.2006-0814

Søndergaard, 2012, Body composition determines direct ffa storage pattern in overweight women, Am J Physiol Endocrinol Metab, 302, E1599, 10.1152/ajpendo.00015.2012

Jensen, 2008, Role of body fat distribution and the metabolic complications of obesity, J Clin Endocrinol Metab, 93, S57, 10.1210/jc.2008-1585

Fu, 2018, Circulating osteonectin and adipokine profiles in relation to metabolically healthy obesity in Chinese children: findings from bcams, J Am Heart Assoc, 7, e009169, 10.1161/JAHA.118.009169

Klöting, 2010, Insulin-sensitive obesity, Am J Physiol Endocrinol Metab, 299, E506, 10.1152/ajpendo.00586.2009

Straznicky, 2009, Blunted sympathetic neural response to oral glucose in obese subjects with the insulin-resistant metabolic syndrome, Am J Clin Nutr, 89, 27, 10.3945/ajcn.2008.26299

Genelhu, 2009, Not all obese subjects of multiethnic origin are at similar risk for developing hypertension and type 2 diabetes, Eur J Intern Med, 20, 289, 10.1016/j.ejim.2008.09.009

Ahl, 2015, Adiponectin levels differentiate metabolically healthy vs unhealthy among obese and nonobese white individuals, J Clin Endocrinol Metab, 100, 4172, 10.1210/jc.2015-2765

Weiss, 2005, The Obese insulin-sensitive adolescent: importance of adiponectin and lipid partitioning, J Clin Endocrinol Metab, 90, 3731, 10.1210/jc.2004-2305

Indulekha, 2015, Metabolic obesity, adipocytokines, and inflammatory markers in asian indians–cures-124, Diabetes Technol Ther, 17, 134, 10.1089/dia.2014.0202

Doumatey, 2012, Paradoxical hyperadiponectinemia is associated with the metabolically healthy obese (mho) phenotype in African Americans, J Endocrinol Metab, 2, 51, 10.4021/jem95w

Alizadeh, 2017, Circulating omentin-1 might be associated with metabolic health status in different phenotypes of body size, Arch Endocrinol Metab, 61, 567, 10.1590/2359-3997000000269

Bremer, 2013, Adipose tissue dysfunction in nascent metabolic syndrome, J Obes, 2013, 393192, 10.1155/2013/393192

Xu, 2003, Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance, J Clin Invest, 112, 1821, 10.1172/JCI200319451

Weisberg, 2003, Obesity is associated with macrophage accumulation in adipose tissue, J Clin Invest, 112, 1796, 10.1172/JCI200319246

Han, 2007, Adipocyte-derived serum amyloid a3 and hyaluronan play a role in monocyte recruitment and adhesion, Diabetes, 56, 2260, 10.2337/db07-0218

Haase, 2014, Local proliferation of macrophages in adipose tissue during obesity-induced inflammation, Diabetologia, 57, 562, 10.1007/s00125-013-3139-y

Bourlier, 2008, Remodeling phenotype of human subcutaneous adipose tissue macrophages, Circulation, 117, 806, 10.1161/CIRCULATIONAHA.107.724096

Cancello, 2006, Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity, Diabetes, 55, 1554, 10.2337/db06-0133

Subramanian, 2008, Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese ldl receptor-deficient mice, Arterioscler Thromb Vasc Biol, 28, 685, 10.1161/ATVBAHA.107.157685

Murano, 2008, Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice, J Lipid Res, 49, 1562, 10.1194/jlr.M800019-JLR200

Harman-Boehm, 2007, Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity, J Clin Endocrinol Metab, 92, 2240, 10.1210/jc.2006-1811

Lumeng, 2007, Obesity induces a phenotypic switch in adipose tissue macrophage polarization, J Clin Invest, 117, 175, 10.1172/JCI29881

Wentworth, 2010, Pro-inflammatory cd11c+cd206+ adipose tissue macrophages are associated with insulin resistance in human obesity, Diabetes, 59, 1648, 10.2337/db09-0287

Lumeng, 2007, Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity, Diabetes, 56, 16, 10.2337/db06-1076

Morris, 2011, Adipose tissue macrophages: phenotypic plasticity and diversity in lean and obese states, Curr Opin Clin Nutr Metab Care, 14, 341, 10.1097/MCO.0b013e328347970b

Kratz, 2014, Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages, Cell Metab, 20, 614, 10.1016/j.cmet.2014.08.010

Winer, 2009, Normalization of obesity-associated insulin resistance through immunotherapy, Nat Med, 15, 921, 10.1038/nm.2001

O'Rourke, 2009, Depot-specific differences in inflammatory mediators and a role for nk cells and ifn-gamma in inflammation in human adipose tissue, Int J Obes, 33, 978, 10.1038/ijo.2009.133

Rocha, 2008, Interferon-gamma, a th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity, Circ Res, 103, 467, 10.1161/CIRCRESAHA.108.177105

Bendelac, 2007, The biology of nkt cells, Annu Rev Immunol, 25, 297, 10.1146/annurev.immunol.25.022106.141711

Godfrey, 2010, Raising the nkt cell family, Nat Immunol, 11, 197, 10.1038/ni.1841

Kronenberg, 2005, Toward an understanding of nkt cell biology: progress and paradoxes, Annu Rev Immunol, 23, 877, 10.1146/annurev.immunol.23.021704.115742

Ji, 2012, Activation of natural killer t cells promotes m2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (il-4)/stat6 protein signaling axis in obesity, J Biol Chem, 287, 13561, 10.1074/jbc.M112.350066

Lynch, 2012, Adipose tissue invariant nkt cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production, Immunity, 37, 574, 10.1016/j.immuni.2012.06.016

Lynch, 2009, Invariant nkt cells and cd1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity, Eur J Immunol, 39, 1893, 10.1002/eji.200939349

Schipper, 2012, Natural killer t cells in adipose tissue prevent insulin resistance, J Clin Invest, 122, 3343, 10.1172/JCI62739

Winer, 2011, B cells promote insulin resistance through modulation of t cells and production of pathogenic igg antibodies, Nat Med, 17, 610, 10.1038/nm.2353

Liu, 2009, Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice, Nat Med, 15, 940, 10.1038/nm.1994

Cho, 2016, Adipose tissue dendritic cells are independent contributors to obesity-induced inflammation and insulin resistance, J Immunol, 197, 3650, 10.4049/jimmunol.1600820

Sundara Rajan, 2016, Dendritic cells and adipose tissue, Immunology, 149, 353, 10.1111/imm.12653

Mortensen, 2001, C-reactive protein, inflammation, and innate immunity, Immunol Res, 24, 163, 10.1385/IR:24:2:163

Yudkin, 2000, Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?, Atherosclerosis, 148, 209, 10.1016/S0021-9150(99)00463-3

Schmidt-Arras, 2016, Il-6 pathway in the liver: from physiopathology to therapy, J Hepatol, 64, 1403, 10.1016/j.jhep.2016.02.004

Visser, 1999, Elevated c-reactive protein levels in overweight and obese adults, JAMA, 282, 2131, 10.1001/jama.282.22.2131

Yang, 2006, Acute-phase serum amyloid a: an inflammatory adipokine and potential link between obesity and its metabolic complications, PLoS Med, 3, e287, 10.1371/journal.pmed.0030287

Uemura, 2017, Relationships of serum high-sensitivity c-reactive protein and body size with insulin resistance in a japanese cohort, PLoS ONE, 12, e0178672, 10.1371/journal.pone.0178672

González, 2006, Metabolic syndrome, insulin resistance and the inflammation markers c-reactive protein and ferritin, Eur J Clin Nutr, 60, 802, 10.1038/sj.ejcn.1602384

Cozlea, 2013, The impact of c reactive protein on global cardiovascular risk on patients with coronary artery disease, Curr Health Sci J, 39, 225

Filippin-Monteiro, 2012, Serum amyloid a is a growth factor for 3t3-l1 adipocytes, inhibits differentiation and promotes insulin resistance, Int J Obes, 36, 1032, 10.1038/ijo.2011.193

Johnson, 2004, Serum amyloid a as a predictor of coronary artery disease and cardiovascular outcome in women: The national heart, lung, and blood institute-sponsored women's ischemia syndrome evaluation (wise), Circulation, 109, 726, 10.1161/01.CIR.0000115516.54550.B1

Targonska-Stepniak, 2014, Serum amyloid a as a marker of persistent inflammation and an indicator of cardiovascular and renal involvement in patients with rheumatoid arthritis, Mediators Inflamm, 2014, 793628, 10.1155/2014/793628

Getz, 2016, Serum amyloid a and atherosclerosis, Curr Opin Lipidol, 27, 531, 10.1097/MOL.0000000000000331

Lewis, 2004, Increase in serum amyloid a evoked by dietary cholesterol is associated with increased atherosclerosis in mice, Circulation, 110, 540, 10.1161/01.CIR.0000136819.93989.E1

Meek, 1994, Expression of apolipoprotein serum amyloid a mRNA in human atherosclerotic lesions and cultured vascular cells: implications for serum amyloid a function, Proc Natl Acad Sci USA, 91, 3186, 10.1073/pnas.91.8.3186

Bastard, 2000, Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss, J Clin Endocrinol Metab, 85, 3338, 10.1210/jcem.85.9.6839

Pickup, 2000, Plasma interleukin-6, tumour necrosis factor alpha and blood cytokine production in type 2 diabetes, Life Sci, 67, 291, 10.1016/S0024-3205(00)00622-6

Mohamed-Ali, 1997, Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo, J Clin Endocrinol Metab, 82, 4196, 10.1210/jc.82.12.4196

Yeop Han, 2010, Differential effect of saturated and unsaturated free fatty acids on the generation of monocyte adhesion and chemotactic factors by adipocytes: dissociation of adipocyte hypertrophy from inflammation, Diabetes, 59, 386, 10.2337/db09-0925

Zhang, 2014, Adipocyte lipolysis-stimulated interleukin-6 production requires sphingosine kinase 1 activity, J Biol Chem, 289, 32178, 10.1074/jbc.M114.601096

Matsubara, 2012, Pgrn is a key adipokine mediating high fat diet-induced insulin resistance and obesity through il-6 in adipose tissue, Cell Metab, 15, 38, 10.1016/j.cmet.2011.12.002

Fried, 1998, Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid, J Clin Endocrinol Metab, 83, 847, 10.1210/jc.83.3.847

Carey, 1996, Abdominal fat and insulin resistance in normal and overweight women: direct measurements reveal a strong relationship in subjects at both low and high risk of niddm, Diabetes, 45, 633, 10.2337/diabetes.45.5.633

Sabio, 2008, A stress signaling pathway in adipose tissue regulates hepatic insulin resistance, Science, 322, 1539, 10.1126/science.1160794

Rotter, 2003, Interleukin-6 (Il-6) induces insulin resistance in 3t3-l1 adipocytes and is, like il-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects, J Biol Chem, 278, 45777, 10.1074/jbc.M301977200

Wunderlich, 2010, Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action, Cell Metab, 12, 237, 10.1016/j.cmet.2010.06.011

Braune, 2017, Il-6 regulates m2 polarization and local proliferation of adipose tissue macrophages in obesity, J Immunol, 198, 2927, 10.4049/jimmunol.1600476

Hotamisligil, 1993, Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance, Science, 259, 87, 10.1126/science.7678183

Kern, 2001, Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance, Am J Physiol Endocrinol Metab, 280, E745, 10.1152/ajpendo.2001.280.5.E745

Zahorska-Markiewicz, 2000, Serum concentrations of tnf-alpha and soluble tnf-alpha receptors in obesity, Int J Obes Relat Metab Disord, 24, 1392, 10.1038/sj.ijo.0801398

Zahorska-Markiewicz, 2006, Metabolic effects associated with adipose tissue distribution, Adv Med Sci, 51, 111

Paz, 1997, A molecular basis for insulin resistance. Elevated serine/threonine phosphorylation of irs-1 and irs-2 inhibits their binding to the juxtamembrane region of the insulin receptor and impairs their ability to undergo insulin-induced tyrosine phosphorylation, J Biol Chem, 272, 29911, 10.1074/jbc.272.47.29911

Wellen, 2003, Obesity-induced inflammatory changes in adipose tissue, J Clin Invest, 112, 1785, 10.1172/JCI20514

Weisberg, 2006, Ccr2 modulates inflammatory and metabolic effects of high-fat feeding, J Clin Invest, 116, 115, 10.1172/JCI24335

Christiansen, 2005, Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects, Int J Obes, 29, 146, 10.1038/sj.ijo.0802839

Kanda, 2006, Mcp-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity, J Clin Invest, 116, 1494, 10.1172/JCI26498

Sartipy, 2003, Monocyte chemoattractant protein 1 in obesity and insulin resistance, Proc Natl Acad Sci USA, 100, 7265, 10.1073/pnas.1133870100

Bruun, 2005, Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (at): implication of macrophages resident in the at, J Clin Endocrinol Metab, 90, 2282, 10.1210/jc.2004-1696

Poitou, 2005, Serum amyloid a: production by human white adipocyte and regulation by obesity and nutrition, Diabetologia, 48, 519, 10.1007/s00125-004-1654-6

Poitou, 2006, Serum amyloid a: a marker of adiposity-induced low-grade inflammation but not of metabolic status, Obesity, 14, 309, 10.1038/oby.2006.40

Lappalainen, 2008, Serum concentrations and expressions of serum amyloid a and leptin in adipose tissue are interrelated: the genobin study, Eur J Endocrinol, 158, 333, 10.1530/EJE-07-0598

Trayhurn, 2004, Adipokines: inflammation and the pleiotropic role of white adipose tissue, Br J Nutr, 92, 347, 10.1079/BJN20041213

Gómez-Ambrosi, 2006, Increased serum amyloid a concentrations in morbid obesity decrease after gastric bypass, Obes Surg, 16, 262, 10.1381/096089206776116525

den Hartigh, 2014, Deletion of serum amyloid a3 improves high fat high sucrose diet-induced adipose tissue inflammation and hyperlipidemia in female mice, PLoS ONE, 9, e108564, 10.1371/journal.pone.0108564

Sjöholm, 2005, A microarray search for genes predominantly expressed in human omental adipocytes: adipose tissue as a major production site of serum amyloid a, J Clin Endocrinol Metab, 90, 2233, 10.1210/jc.2004-1830

Rutkowski, 2015, The cell biology of fat expansion, J Cell Biol, 208, 501, 10.1083/jcb.201409063

Krssak, 1999, Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1h nmr spectroscopy study, Diabetologia, 42, 113, 10.1007/s001250051123

Wajchenberg, 2000, Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome, Endocr Rev, 21, 697, 10.1210/edrv.21.6.0415

Yu, 2002, Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (irs-1)-associated phosphatidylinositol 3-kinase activity in muscle, J Biol Chem, 277, 50230, 10.1074/jbc.M200958200

Itani, 2002, Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase c, and ikappab-alpha, Diabetes, 51, 2005, 10.2337/diabetes.51.7.2005

Turinsky, 1990, 1,2-diacylglycerol and ceramide levels in insulin-resistant tissues of the rat in vivo, J Biol Chem, 265, 16880, 10.1016/S0021-9258(17)44844-7

Holl, 2007, Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance, Cell Metab, 5, 167, 10.1016/j.cmet.2007.01.002

Fabbrini, 2009, Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity, Proc Natl Acad Sci USA, 106, 15430, 10.1073/pnas.0904944106

Korenblat, 2008, Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects, Gastroenterology, 134, 1369, 10.1053/j.gastro.2008.01.075

Magkos, 2010, Increased whole-body adiposity without a concomitant increase in liver fat is not associated with augmented metabolic dysfunction, Obesity, 18, 1510, 10.1038/oby.2010.90

Kabir, 2005, Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance, Am J Physiol Endocrinol Metab, 288, E454, 10.1152/ajpendo.00203.2004

Donnelly, 2005, Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease, J Clin Invest, 115, 1343, 10.1172/JCI23621

Perry, 2014, The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes, Nature, 510, 84, 10.1038/nature13478

Stratford, 2004, Regulation of insulin action by ceramide: dual mechanisms linking ceramide accumulation to the inhibition of akt/protein kinase b, J Biol Chem, 279, 36608, 10.1074/jbc.M406499200

Blouin, 2010, Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling, Diabetes, 59, 600, 10.2337/db09-0897

Xia, 2015, Targeted induction of ceramide degradation leads to improved systemic metabolism and reduced hepatic steatosis, Cell Metab, 22, 266, 10.1016/j.cmet.2015.06.007

Liu, 2012, Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism, Proc Natl Acad Sci USA, 109, 14568, 10.1073/pnas.1211611109

Ruan, 2016, Adiponectin signaling and function in insulin target tissues, J Mol Cell Biol, 8, 101, 10.1093/jmcb/mjw014

Yamauchi, 2002, Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating amp-activated protein kinase, Nat Med, 8, 1288, 10.1038/nm788

Bézaire, 2009, Chronic tnfalpha and camp pre-treatment of human adipocytes alter hsl, atgl and perilipin to regulate basal and stimulated lipolysis, FEBS Lett, 583, 3045, 10.1016/j.febslet.2009.08.019

Laurencikiene, 2007, Nf-kappab is important for tnf-alpha-induced lipolysis in human adipocytes, J Lipid Res, 48, 1069, 10.1194/jlr.M600471-JLR200

Gregory, 2002, Neutrophil-kupffer cell interaction: a critical component of host defenses to systemic bacterial infections, J Leukoc Biol, 72, 239, 10.1189/jlb.72.2.239

Baffy, 2009, Kupffer cells in non-alcoholic fatty liver disease: the emerging view, J Hepatol, 51, 212, 10.1016/j.jhep.2009.03.008

Dey, 2014, Ontogeny and polarization of macrophages in inflammation: blood monocytes versus tissue macrophages, Front Immunol, 5, 683, 10.3389/fimmu.2014.00683

Shoelson, 2006, Inflammation and insulin resistance, J Clin Invest, 116, 1793, 10.1172/JCI29069

Jager, 2016, Liver innate immune cells and insulin resistance: the multiple facets of kupffer cells, J Intern Med, 280, 209, 10.1111/joim.12483

Tosello-Trampont, 2012, Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-α production, J Biol Chem, 287, 40161, 10.1074/jbc.M112.417014

Gallagher, 2005, Adipose tissue in muscle: a novel depot similar in size to visceral adipose tissue, Am J Clin Nutr, 81, 903, 10.1093/ajcn/81.4.903

Bachmann, 2001, Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans, Diabetes, 50, 2579, 10.2337/diabetes.50.11.2579

Sciorati, 2015, Fat deposition and accumulation in the damaged and inflamed skeletal muscle: cellular and molecular players, Cell Mol Life Sci, 72, 2135, 10.1007/s00018-015-1857-7

Addison, 2014, Intermuscular fat: a review of the consequences and causes, Int J Endocrinol, 2014, 309570, 10.1155/2014/309570

Kim, 2017, Intermuscular adipose tissue content and intramyocellular lipid fatty acid saturation are associated with glucose homeostasis in middle-aged and older adults, Endocrinol Metab, 32, 257, 10.3803/EnM.2017.32.2.257

Goodpaster, 2000, Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus, Am J Clin Nutr, 71, 885, 10.1093/ajcn/71.4.885

Oakes, 1997, Mechanisms of liver and muscle insulin resistance induced by chronic high-fat feeding, Diabetes, 46, 1768, 10.2337/diabetes.46.11.1768

Goodpaster, 1998, Role of muscle in triglyceride metabolism, Curr Opin Lipidol, 9, 231, 10.1097/00041433-199806000-00008

Granados, 2019, Association of abdominal muscle composition with prediabetes and diabetes: the cardia study, Diabetes Obes Metab, 21, 267, 10.1111/dom.13513

Haykowsky, 2018, Regional adipose distribution and its relationship to exercise intolerance in older obese patients who have heart failure with preserved ejection fraction, JACC Heart Fail, 6, 640, 10.1016/j.jchf.2018.06.002

Terry, 2017, Intermuscular adipose tissue and subclinical coronary artery calcification in midlife: the cardia study (coronary artery risk development in young adults), Arterioscler Thromb Vasc Biol, 37, 2370, 10.1161/ATVBAHA.117.309633

Yim, 2007, Intermuscular adipose tissue rivals visceral adipose tissue in independent associations with cardiovascular risk, Int J Obes, 31, 1400, 10.1038/sj.ijo.0803621

Ferrara, 2019, Impact of different ectopic fat depots on cardiovascular and metabolic diseases, J Cell Physiol, 234, 21630, 10.1002/jcp.28821

Yafei, 2019, Echocardiographic association of epicardial fat with carotid intima-media thickness in patients with type 2 diabetes, Diab Vasc Dis Res, 16, 378, 10.1177/1479164119827602

Calcaterra, 2018, Epicardial fat thickness in non-obese neurologically impaired children: association with unfavorable cardiometabolic risk profile, Ann Nutr Metab, 72, 96, 10.1159/000484326

Rabkin, 2014, The relationship between epicardial fat and indices of obesity and the metabolic syndrome: a systematic review and meta-analysis, Metab Syndr Relat Disord, 12, 31, 10.1089/met.2013.0107

Christensen, 2019, Epicardial adipose tissue predicts incident cardiovascular disease and mortality in patients with type 2 diabetes, Cardiovasc Diabetol, 18, 114, 10.1186/s12933-019-0917-y

Lopaschuk, 2007, Cardiac energy metabolism in obesity, Circ Res, 101, 335, 10.1161/CIRCRESAHA.107.150417

Iozzo, 2011, Myocardial, perivascular, and epicardial fat, Diabetes Care, 34, S371, 10.2337/dc11-s250

Nosalski, 2017, Perivascular adipose tissue inflammation in vascular disease, Br J Pharmacol, 174, 3496, 10.1111/bph.13705

Fitzgibbons, 2011, Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation, Am J Physiol Heart Circ Physiol, 301, H1425, 10.1152/ajpheart.00376.2011

Xia, 2017, Restoration of perivascular adipose tissue function in diet-induced obese mice without changing bodyweight, Br J Pharmacol, 174, 3443, 10.1111/bph.13703

Costa, 2018, Perivascular adipose tissue as a relevant fat depot for cardiovascular risk in obesity, Front Physiol, 9, 253, 10.3389/fphys.2018.00253

Takaoka, 2009, Periadventitial adipose tissue plays a critical role in vascular remodeling, Circ Res, 105, 906, 10.1161/CIRCRESAHA.109.199653

Gaborit, 2015, Human epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri-coronary location, Cardiovasc Res, 108, 62, 10.1093/cvr/cvv208

Nasarre, 2014, Low density lipoprotein receptor-related protein 1 is upregulated in epicardial fat from type 2 diabetes mellitus patients and correlates with glucose and triglyceride plasma levels, Acta Diabetol, 51, 23, 10.1007/s00592-012-0436-8

Uygun, 2015, The effect of fatty pancreas on serum glucose parameters in patients with nonalcoholic steatohepatitis, Eur J Intern Med, 26, 37, 10.1016/j.ejim.2014.11.007

Heni, 2010, Pancreatic fat is negatively associated with insulin secretion in individuals with impaired fasting glucose and/or impaired glucose tolerance: a nuclear magnetic resonance study, Diabetes Metab Res Rev, 26, 200, 10.1002/dmrr.1073

Steven, 2016, Weight loss decreases excess pancreatic triacylglycerol specifically in type 2 diabetes, Diabetes Care, 39, 158, 10.2337/dc15-0750

Wong, 2014, Fatty pancreas, insulin resistance, and β-cell function: a population study using fat-water magnetic resonance imaging, Am J Gastroenterol, 109, 589, 10.1038/ajg.2014.1

Wang, 2014, Enigmatic ectopic fat: prevalence of nonalcoholic fatty pancreas disease and its associated factors in a chinese population, J Am Heart Assoc, 3, e000297, 10.1161/JAHA.113.000297

Pinnick, 2008, Pancreatic ectopic fat is characterized by adipocyte infiltration and altered lipid composition, Obesity, 16, 522, 10.1038/oby.2007.110

Navina, 2011, Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity, Sci Transl Med, 3, 107ra110, 10.1126/scitranslmed.3002573

Noel, 2016, Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections, Gut, 65, 100, 10.1136/gutjnl-2014-308043

Yoneshiro, 2011, Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans, Obesity, 9, 1755, 10.1038/oby.2011.125

Wang, 2015, Brown adipose tissue activation is inversely related to central obesity and metabolic parameters in adult human, PLoS ONE, 10, e0123795, 10.1371/journal.pone.0123795

Brendle, 2018, Correlation of brown adipose tissue with other body fat compartments and patient characteristics: a retrospective analysis in a large patient cohort using pet/ct, Acad Radiol, 25, 102, 10.1016/j.acra.2017.09.007

Saito, 2009, High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity, Diabetes, 58, 1526, 10.2337/db09-0530

Matsushita, 2014, Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans, Int J Obes, 38, 812, 10.1038/ijo.2013.206

Hanssen, 2015, Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus, Nat Med, 21, 863, 10.1038/nm.3891

Hanssen, 2015, Short-term cold acclimation recruits brown adipose tissue in obese humans, Diabetes, 65, 1179, 10.2337/db15-1372

Villarroya, 2018, Inflammation of brown/beige adipose tissues in obesity and metabolic disease, J Intern Med, 284, 492, 10.1111/joim.12803

Ferré, 1986, Glucose utilization in vivo and insulin-sensitivity of rat brown adipose tissue in various physiological and pathological conditions, Biochem J, 233, 249, 10.1042/bj2330249

Orava, 2013, Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans, Obesity, 21, 2279, 10.1002/oby.20456

Nedergaard, 2011, New powers of brown fat: fighting the metabolic syndrome, Cell Metab, 13, 238, 10.1016/j.cmet.2011.02.009

Moonen, 2019, Human brown adipose tissue: underestimated target in metabolic disease?, Biochim Biophys Acta Mol Cell Biol Lipids, 1864, 104, 10.1016/j.bbalip.2018.05.012

Ouellet, 2012, Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans, J Clin Invest, 122, 545, 10.1172/JCI60433

Scheele, 2017, Metabolic regulation and the anti-obesity perspectives of human brown fat, Redox Biol, 12, 770, 10.1016/j.redox.2017.04.011

Sakamoto, 2016, Macrophage infiltration into obese adipose tissues suppresses the induction of ucp1 level in mice, Am J Physiol Endocrinol Metab, 310, E676, 10.1152/ajpendo.00028.2015

Roberts-Toler, 2015, Diet-induced obesity causes insulin resistance in mouse brown adipose tissue, Obesity, 23, 1765, 10.1002/oby.21134

Bae, 2014, Activation of pattern recognition receptors in brown adipocytes induces inflammation and suppresses uncoupling protein 1 expression and mitochondrial respiration, Am J Physiol Cell Physiol, 306, C918, 10.1152/ajpcell.00249.2013

Martins, 2017, Thermogenesis, fatty acid synthesis with oxidation, and inflammation in the brown adipose tissue of ob/ob (-/-) mice, Ann Anat, 210, 44, 10.1016/j.aanat.2016.11.013

Chiang, 2009, The protein kinase ikkepsilon regulates energy balance in obese mice, Cell, 138, 961, 10.1016/j.cell.2009.06.046

Kumari, 2016, Irf3 promotes adipose inflammation and insulin resistance and represses browning, J Clin Invest, 126, 2839, 10.1172/JCI86080

Estève, 2015, Human white and brite adipogenesis is supported by msca1 and is impaired by immune cells, Stem Cells, 33, 1277, 10.1002/stem.1916

Kahn, 2006, Mechanisms linking obesity to insulin resistance and type 2 diabetes, Nature, 444, 840, 10.1038/nature05482

Burhans, 2018, Contribution of adipose tissue inflammation to the development of type 2 diabetes mellitus, Compr Physiol, 9, 1, 10.1002/cphy.c170040

Raji, 2001, Body fat distribution and insulin resistance in healthy asian indians and caucasians, J Clin Endocrinol Metab, 86, 5366, 10.1210/jcem.86.11.7992

Paradisi, 1999, Dual energy x-ray absorptiometry assessment of fat mass distribution and its association with the insulin resistance syndrome, Diabetes Care, 22, 1310, 10.2337/diacare.22.8.1310

Mittendorfer, 2009, Relationship between body fat mass and free fatty acid kinetics in men and women, Obesity, 17, 1872, 10.1038/oby.2009.224

Björntorp, 1969, Plasma free fatty acid turnover rate in obesity, Acta Med Scand, 185, 351, 10.1111/j.0954-6820.1969.tb07347.x

Jensen, 1989, Influence of body fat distribution on free fatty acid metabolism in obesity, J Clin Invest, 83, 1168, 10.1172/JCI113997

Reaven, 1988, Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with niddm, Diabetes, 37, 1020, 10.2337/diabetes.37.8.1020

Ferrannini, 1997, Insulin action and non-esterified fatty acids. The European group for the study of insulin resistance (egir), Proc Nutr Soc, 56, 753, 10.1079/PNS19970076

Succurro, 2008, Insulin secretion in metabolically obese, but normal weight, and in metabolically healthy but obese individuals, Obesity, 16, 1881, 10.1038/oby.2008.308

Swarbrick, 2008, Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans, Metab Syndr Relat Disord, 6, 87, 10.1089/met.2007.0029

Yamauchi, 2001, The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity, Nat Med, 7, 941, 10.1038/90984

Arita, 1999, Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity, Biochem Biophys Res Commun, 257, 79, 10.1006/bbrc.1999.0255

Hotta, 2000, Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients, Arterioscler Thromb Vasc Biol, 20, 1595, 10.1161/01.ATV.20.6.1595

Weyer, 2001, Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia, J Clin Endocrinol Metab, 86, 1930, 10.1210/jcem.86.5.7463

Bobbert, 2013, Fibroblast growth factor 21 predicts the metabolic syndrome and type 2 diabetes in caucasians, Diabetes Care, 36, 145, 10.2337/dc12-0703

Markan, 2016, Metabolic fibroblast growth factors (fgfs): mediators of energy homeostasis, Semin Cell Dev Biol, 53, 85, 10.1016/j.semcdb.2015.09.021

Li, 2018, Fibroblast growth factor 21 increases insulin sensitivity through specific expansion of subcutaneous fat, Nat Commun, 9, 272, 10.1038/s41467-017-02677-9

Hale, 2012, Lack of overt fgf21 resistance in two mouse models of obesity and insulin resistance, Endocrinology, 153, 69, 10.1210/en.2010-1262

Kharitonenkov, 2005, Fgf-21 as a novel metabolic regulator, J Clin Invest, 115, 1627, 10.1172/JCI23606

Markan, 2018, Defining Fgf21 resistance during obesity: controversy, criteria and unresolved questions, F1000Res, 7, 289, 10.12688/f1000research.14117.1

Gustafson, 2015, Insulin resistance and impaired adipogenesis, Trends Endocrinol Metab, 26, 193, 10.1016/j.tem.2015.01.006

Ghaben, 2019, Adipogenesis and metabolic health, Nat Rev Mol Cell Biol, 20, 242, 10.1038/s41580-018-0093-z

Mariman, 2010, Adipocyte extracellular matrix composition, dynamics and role in obesity, Cell Mol Life Sci, 67, 1277, 10.1007/s00018-010-0263-4

Huber, 2007, Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids, Int J Obes, 31, 1004, 10.1038/sj.ijo.0803511

Khan, 2009, Metabolic dysregulation and adipose tissue fibrosis: role of collagen vi, Mol Cell Biol, 29, 1575, 10.1128/MCB.01300-08

Spencer, 2011, Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance, J Clin Endocrinol Metab, 96, E1990, 10.1210/jc.2011-1567

Roedig, 2019, Breaking down chronic inflammatory diseases: the role of biglycan in promoting a switch between inflammation and autophagy, FEBS J, 286, 2965, 10.1111/febs.14791

Wight, 2014, Versican and the control of inflammation, Matrix Biol, 35, 152, 10.1016/j.matbio.2014.01.015

Sun, 2014, Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction, Nat Commun, 5, 3485, 10.1038/ncomms4485

Leibel, 1989, Physiologic basis for the control of body fat distribution in humans, Annu Rev Nutr, 9, 417, 10.1146/annurev.nu.09.070189.002221

Bonora, 2000, Relationship between regional fat distribution and insulin resistance, Int J Obes Relat Metab Disord, 24, S32, 10.1038/sj.ijo.0801274

Araneta, 2005, Ethnic differences in visceral adipose tissue and type 2 diabetes: filipino, African-American, and white women, Obes Res, 13, 1458, 10.1038/oby.2005.176

Kotronen, 2011, Comparison of the relative contributions of intra-abdominal and liver fat to components of the metabolic syndrome, Obesity, 19, 23, 10.1038/oby.2010.137

Blüher, 2012, Are there still healthy obese patients?, Curr Opin Endocrinol Diabetes Obes, 19, 341, 10.1097/MED.0b013e328357f0a3

Thomas, 2012, The missing risk: mri and mrs phenotyping of abdominal adiposity and ectopic fat, Obesity, 20, 76, 10.1038/oby.2011.142

Zhang, 2015, Associations of different adipose tissue depots with insulin resistance: a systematic review and meta-analysis of observational studies, Sci Rep, 5, 18495, 10.1038/srep18495

Lopes, 2016, Visceral adiposity syndrome, Diabetol Metab Syndr, 8, 40, 10.1186/s13098-016-0156-2

Manolopoulos, 2010, Gluteofemoral body fat as a determinant of metabolic health, Int J Obes, 34, 949, 10.1038/ijo.2009.286

Tchkonia, 2013, Mechanisms and metabolic implications of regional differences among fat depots, Cell Metab, 17, 644, 10.1016/j.cmet.2013.03.008

McLaughlin, 2011, Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity, J Clin Endocrinol Metab, 96, E1756, 10.1210/jc.2011-0615

Klein, 2004, Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease, N Engl J Med, 350, 2549, 10.1056/NEJMoa033179

Tran, 2008, Beneficial effects of subcutaneous fat transplantation on metabolism, Cell Metab, 7, 410, 10.1016/j.cmet.2008.04.004

Liu, 2013, Brown adipose tissue transplantation improves whole-body energy metabolism, Cell Res, 23, 851, 10.1038/cr.2013.64

Stanford, 2013, Brown adipose tissue regulates glucose homeostasis and insulin sensitivity, J Clin Invest, 123, 215, 10.1172/JCI62308

Zhu, 2014, Enhanced sympathetic activity in mice with brown adipose tissue transplantation (transbatation), Physiol Behav, 125, 21, 10.1016/j.physbeh.2013.11.008

Ma, 1986, Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo, Can J Physiol Pharmacol, 64, 609, 10.1139/y86-101

Loyd, 2014, Brown fat fuel use and regulation of energy homeostasis, Curr Opin Clin Nutr Metab Care, 17, 368, 10.1097/MCO.0000000000000063

Lee, 2010, A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans, Am J Physiol Endocrinol Metab, 299, E601, 10.1152/ajpendo.00298.2010

Orava, 2011, Different metabolic responses of human brown adipose tissue to activation by cold and insulin, Cell Metab, 14, 272, 10.1016/j.cmet.2011.06.012

Dallner, 2006, Beta3-adrenergic receptors stimulate glucose uptake in brown adipocytes by two mechanisms independently of glucose transporter 4 translocation, Endocrinology, 147, 5730, 10.1210/en.2006-0242

Mössenböck, 2014, Browning of white adipose tissue uncouples glucose uptake from insulin signaling, PLoS ONE, 9, e110428, 10.1371/journal.pone.0110428

Olsen, 2014, Glucose uptake in brown fat cells is dependent on mtor complex 2-promoted glut1 translocation, J Cell Biol, 207, 365, 10.1083/jcb.201403080

Peirce, 2013, Regulation of glucose homoeostasis by brown adipose tissue, Lancet Diabetes Endocrinol, 1, 353, 10.1016/S2213-8587(13)70055-X

Kaisanlahti, 2019, Browning of white fat: agents and implications for beige adipose tissue to type 2 diabetes, J Physiol Biochem, 75, 1, 10.1007/s13105-018-0658-5

Chondronikola, 2014, Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans, Diabetes, 63, 4089, 10.2337/db14-0746

Eckel, 1998, American heart association call to action: obesity as a major risk factor for coronary heart disease. Aha nutrition committee, Circulation, 97, 2099, 10.1161/01.CIR.97.21.2099

Stefan, 2018, Metabolically healthy obesity: the low-hanging fruit in obesity treatment?, Lancet Diabetes Endocrinol, 6, 249, 10.1016/S2213-8587(17)30292-9

Wang, 2015, Association of body mass index with mortality and cardiovascular events for patients with coronary artery disease: a systematic review and meta-analysis, Heart, 101, 1631, 10.1136/heartjnl-2014-307119

Horwich, 2018, Obesity and the obesity paradox in heart failure, Prog Cardiovasc Dis, 61, 151, 10.1016/j.pcad.2018.05.005

Lavie, 2009, Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss, J Am Coll Cardiol, 53, 1925, 10.1016/j.jacc.2008.12.068

St-Pierre, 2002, Contribution of abdominal obesity and hypertriglyceridemia to impaired fasting glucose and coronary artery disease, Am J Cardiol, 90, 15, 10.1016/S0002-9149(02)02378-0

Grundy, 2004, Definition of metabolic syndrome: Report of the national heart, lung, and blood institute/American heart association conference on scientific issues related to definition, Circulation, 109, 433, 10.1161/01.CIR.0000111245.75752.C6

Haffner, 2006, Relationship of metabolic risk factors and development of cardiovascular disease and diabetes, Obesity, 14, 121S, 10.1038/oby.2006.291

Alberti, 2009, Harmonizing the metabolic syndrome: A joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity, Circulation, 120, 1640, 10.1161/CIRCULATIONAHA.109.192644

Paolisso, 1995, A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of niddm, Diabetologia, 38, 1213, 10.1007/s001250050414

Santomauro, 1999, Overnight lowering of free fatty acids with acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects, Diabetes, 48, 1836, 10.2337/diabetes.48.9.1836

Dutheil, 2018, Cardiovascular risk of adipokines: a review, J Int Med Res, 46, 2082, 10.1177/0300060517706578

Matsuzawa, 2006, The metabolic syndrome and adipocytokines, FEBS Lett, 580, 2917, 10.1016/j.febslet.2006.04.028

Hopkins, 2007, Adiponectin actions in the cardiovascular system, Cardiovasc Res, 74, 11, 10.1016/j.cardiores.2006.10.009

Qiao, 2008, Adiponectin reduces plasma triglyceride by increasing vldl triglyceride catabolism, Diabetes, 57, 1824, 10.2337/db07-0435

Aldhahi, 2003, Adipokines, inflammation, and the endothelium in diabetes, Curr Diab Rep, 3, 293, 10.1007/s11892-003-0020-2

Yuhki, 2005, Fat, keeping the heart healthy?, Nat Med, 11, 1048, 10.1038/nm1005-1048

Chen, 2003, Adiponectin stimulates production of nitric oxide in vascular endothelial cells, J Biol Chem, 278, 45021, 10.1074/jbc.M307878200

Du, 2016, Adiponectin at physiologically relevant concentrations enhances the vasorelaxative effect of acetylcholine via cav-1/adipor-1 signaling, PLoS ONE, 11, e0152247, 10.1371/journal.pone.0152247

Sahu, 2003, Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance, Front Neuroendocrinol, 24, 225, 10.1016/j.yfrne.2003.10.001

Söderberg, 1999, Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort, Stroke, 30, 328, 10.1161/01.STR.30.2.328

Söderberg, 1999, Leptin is associated with increased risk of myocardial infarction, J Intern Med, 246, 409, 10.1046/j.1365-2796.1999.00571.x

Wallace, 2001, Plasma leptin and the risk of cardiovascular disease in the west of scotland coronary prevention study (woscops), Circulation, 104, 3052, 10.1161/hc5001.101061

Schulze, 2003, Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure, Eur J Heart Fail, 5, 33, 10.1016/S1388-9842(02)00177-0

Paolisso, 1999, Plasma leptin level is associated with myocardial wall thickness in hypertensive insulin-resistant men, Hypertension, 34, 1047, 10.1161/01.HYP.34.5.1047

Lehrke, 2004, An inflammatory cascade leading to hyperresistinemia in humans, PLoS Med, 1, e45, 10.1371/journal.pmed.0010045

Verma, 2003, Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction, Circulation, 108, 736, 10.1161/01.CIR.0000084503.91330.49

Calabro, 2004, Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways, Circulation, 110, 3335, 10.1161/01.CIR.0000147825.97879.E7

Reilly, 2005, Resistin is an inflammatory marker of atherosclerosis in humans, Circulation, 111, 932, 10.1161/01.CIR.0000155620.10387.43

Ouchi, 1999, Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin, Circulation, 100, 2473, 10.1161/01.CIR.100.25.2473

Fatkhullina, 2016, The role of cytokines in the development of atherosclerosis, Biochemistry (Mosc), 81, 1358, 10.1134/S0006297916110134

Burstein, 1996, Cytokine-induced alteration of platelet and hemostatic function, Stem Cells, 14, 154, 10.1002/stem.5530140720

Bhagat, 1997, Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo, Circulation, 96, 3042, 10.1161/01.CIR.96.9.3042

Ridker, 2000, C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women, N Engl J Med, 342, 836, 10.1056/NEJM200003233421202

Ong, 2015, The relationship of fibroblast growth factor 21 with cardiovascular outcome events in the fenofibrate intervention and event lowering in diabetes study, Diabetologia, 58, 464, 10.1007/s00125-014-3458-7

Ong, 2018, Association of elevated circulating fibroblast growth factor 21 levels with prevalent and incident metabolic syndrome: the multi-ethnic study of atherosclerosis, Atherosclerosis, 281, 10.1016/j.atherosclerosis.2018.10.011

Domouzoglou, 2015, Fibroblast growth factors in cardiovascular disease: the emerging role of fgf21, Am J Physiol Heart Circ Physiol, 309, H1029, 10.1152/ajpheart.00527.2015

Lin, 2010, Serum levels of fgf-21 are increased in coronary heart disease patients and are independently associated with adverse lipid profile, PLoS ONE, 5, e15534, 10.1371/journal.pone.0015534

Shen, 2013, Additive relationship between serum fibroblast growth factor 21 level and coronary artery disease, Cardiovasc Diabetol, 12, 124, 10.1186/1475-2840-12-124

Ebert, 2018, Relationship between 12 adipocytokines and distinct components of the metabolic syndrome, J Clin Endocrinol Metab, 103, 1015, 10.1210/jc.2017-02085

Lee, 2014, Serum fgf21 concentration is associated with hypertriglyceridaemia, hyperinsulinaemia and pericardial fat accumulation, independently of obesity, but not with current coronary artery status, Clin Endocrinol, 80, 57, 10.1111/cen.12134

Kharitonenkov, 2007, The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21, Endocrinology, 148, 774, 10.1210/en.2006-1168

Gaich, 2013, The effects of ly2405319, an fgf21 analog, in obese human subjects with type 2 diabetes, Cell Metab, 18, 333, 10.1016/j.cmet.2013.08.005

Berg, 2005, Adipose tissue, inflammation, and cardiovascular disease, Circ Res, 96, 939, 10.1161/01.RES.0000163635.62927.34

Forouzandeh, 2013, Does quantifying epicardial and intrathoracic fat with noncontrast computed tomography improve risk stratification beyond calcium scoring alone?, Circ Cardiovasc Imaging, 6, 58, 10.1161/CIRCIMAGING.112.976316

Iacobellis, 2005, Epicardial adipose tissue and insulin resistance in obese subjects, J Clin Endocrinol Metab, 90, 6300, 10.1210/jc.2005-1087

Iacobellis, 2008, Do cardiac and perivascular adipose tissue play a role in atherosclerosis?, Curr Diab Rep, 8, 20, 10.1007/s11892-008-0005-2

Verhagen, 2012, Coronary perivascular adipose tissue characteristics are related to atherosclerotic plaque size and composition. A post-mortem study, Atherosclerosis, 225, 99, 10.1016/j.atherosclerosis.2012.08.031

Fox, 2010, Periaortic fat deposition is associated with peripheral arterial disease: the framingham heart study, Circ Cardiovasc Imaging, 3, 515, 10.1161/CIRCIMAGING.110.958884

Iacobellis, 2003, Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk, J Clin Endocrinol Metab, 88, 5163, 10.1210/jc.2003-030698

Mookadam, 2010, Epicardial fat and its association with cardiovascular risk: a cross-sectional observational study, Heart Views, 11, 103, 10.4103/1995-705X.76801

Nelson, 2011, Epicardial fat: an additional measurement for subclinical atherosclerosis and cardiovascular risk stratification?, J Am Soc Echocardiogr, 24, 339, 10.1016/j.echo.2010.11.008

Gorter, 2008, Relation of epicardial and pericoronary fat to coronary atherosclerosis and coronary artery calcium in patients undergoing coronary angiography, Am J Cardiol, 102, 380, 10.1016/j.amjcard.2008.04.002

Mahabadi, 2010, Association of pericoronary fat volume with atherosclerotic plaque burden in the underlying coronary artery: a segment analysis, Atherosclerosis, 211, 195, 10.1016/j.atherosclerosis.2010.02.013

Lim, 2014, Links between ectopic fat and vascular disease in humans, Arterioscler Thromb Vasc Biol, 34, 1820, 10.1161/ATVBAHA.114.303035

Verhagen, 2011, Perivascular adipose tissue as a cause of atherosclerosis, Atherosclerosis, 214, 3, 10.1016/j.atherosclerosis.2010.05.034

Yudkin, 2005, Vasocrine signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease, Lancet, 365, 1817, 10.1016/S0140-6736(05)66585-3

Sun, 2013, Effect of high free fatty acids on the anti-contractile response of perivascular adipose tissue in rat aorta, J Mol Cell Cardiol, 63, 169, 10.1016/j.yjmcc.2013.07.018

Sacks, 2011, Human epicardial fat: what is new and what is missing?, Clin Exp Pharmacol Physiol, 38, 879, 10.1111/j.1440-1681.2011.05601.x

Kralova Lesna, 2015, Is the amount of coronary perivascular fat related to atherosclerosis?, Physiol Res, 64, S435, 10.33549/physiolres.933151

Ketonen, 2010, Periadventitial adipose tissue promotes endothelial dysfunction via oxidative stress in diet-induced obese c57bl/6 mice, Circ J, 74, 1479, 10.1253/circj.CJ-09-0661

Spiroglou, 2010, Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis, J Atheroscler Thromb, 17, 115, 10.5551/jat.1735

Arangalage, 2019, Epicardial adipose tissue volume is associated with left ventricular remodelling in calcific aortic valve stenosis, Arch Cardiovasc Dis, 112, 594, 10.1016/j.acvd.2019.06.005

Fernández-Alfonso, 2013, Mechanisms of perivascular adipose tissue dysfunction in obesity, Int J Endocrinol, 2013, 402053, 10.1155/2013/402053

Berbée, 2015, Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development, Nat Commun, 6, 6356, 10.1038/ncomms7356

Hung, 2014, Rictor/mtorc2 loss in the myf5 lineage reprograms brown fat metabolism and protects mice against obesity and metabolic disease, Cell Rep, 8, 256, 10.1016/j.celrep.2014.06.007

Bray, 2018, The science of obesity management: an endocrine society scientific statement, Endocr Rev, 39, 79, 10.1210/er.2017-00253

Clifton, 2018, Effects of different weight loss approaches on cvd risk, Curr Atheroscler Rep, 20, 27, 10.1007/s11883-018-0728-8

Harrington, 2009, A review and meta-analysis of the effect of weight loss on all-cause mortality risk, Nutr Res Rev, 22, 93, 10.1017/S0954422409990035

Ross, 1997, Effects of diet- and exercise-induced weight loss on visceral adipose tissue in men and women, Sports Med, 24, 55, 10.2165/00007256-199724010-00005

van Gemert, 2019, Effect of diet with or without exercise on abdominal fat in postmenopausal women - a randomised trial, BMC Public Health, 19, 174, 10.1186/s12889-019-6510-1

Borges, 2019, Exercise training and/or diet on reduction of intra-abdominal adipose tissue and risk factors for cardiovascular disease, Eur J Clin Nutr, 73, 1063, 10.1038/s41430-018-0318-4

Ross, 2000, Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial, Ann Intern Med, 133, 92, 10.7326/0003-4819-133-2-200007180-00008

Janssen, 1999, Effects of sex on the change in visceral, subcutaneous adipose tissue and skeletal muscle in response to weight loss, Int J Obes Relat Metab Disord, 23, 1035, 10.1038/sj.ijo.0801038

Ryan, 2014, Aerobic exercise and weight loss reduce vascular markers of inflammation and improve insulin sensitivity in obese women, J Am Geriatr Soc, 62, 607, 10.1111/jgs.12749

Janssen, 2002, Effects of an energy-restrictive diet with or without exercise on abdominal fat, intermuscular fat, and metabolic risk factors in obese women, Diabetes Care, 25, 431, 10.2337/diacare.25.3.431

Gregg, 2016, Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the look ahead randomised clinical trial, Lancet Diabetes Endocrinol, 4, 913, 10.1016/S2213-8587(16)30162-0

Baum, 2017, Targeting weight loss interventions to reduce cardiovascular complications of type 2 diabetes: a machine learning-based post-hoc analysis of heterogeneous treatment effects in the look ahead trial, Lancet Diabetes Endocrinol, 5, 808, 10.1016/S2213-8587(17)30176-6

Wing, 2010, Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the look ahead trial, Arch Intern Med, 170, 1566, 10.1001/archinternmed.2010.334

Després, 1985, Lack of relationship between changes in adiposity and plasma lipids following endurance training, Atherosclerosis, 54, 135, 10.1016/0021-9150(85)90173-X

Simonsen, 2004, The effect of exercise on regional adipose tissue and splanchnic lipid metabolism in overweight type 2 diabetic subjects, Diabetologia, 47, 652, 10.1007/s00125-004-1374-y

Klein, 1994, Fat metabolism during low-intensity exercise in endurance-trained and untrained men, Am J Physiol, 267, E934, 10.1152/ajpendo.1994.267.6.E934

Gollisch, 2009, Effects of exercise training on subcutaneous and visceral adipose tissue in normal- and high-fat diet-fed rats, Am J Physiol Endocrinol Metab, 297, E495, 10.1152/ajpendo.90424.2008

Poirier, 2001, Exercise in weight management of obesity, Cardiol Clin, 19, 459, 10.1016/S0733-8651(05)70229-0

O'Donovan, 2009, Fat distribution in men of different waist girth, fitness level and exercise habit, Int J Obes, 33, 1356, 10.1038/ijo.2009.189

Lee, 2005, Exercise without weight loss is an effective strategy for obesity reduction in obese individuals with and without type 2 diabetes, J Appl Physiol., 99, 1220, 10.1152/japplphysiol.00053.2005

Stewart, 2005, Exercise and risk factors associated with metabolic syndrome in older adults, Am J Prev Med, 28, 9, 10.1016/j.amepre.2004.09.006

Lee, 2019, Effects of long-term exercise on plasma adipokine levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary dysglycaemic, overweight men and sedentary normoglycaemic men of healthy weight, Diabetologia, 62, 1048, 10.1007/s00125-019-4866-5

Lehnig, 2019, Exercise training induces depot-specific adaptations to white and brown adipose tissue, Science, 11, 425, 10.1016/j.isci.2018.12.033

Sakurai, 2013, The effects of exercise training on obesity-induced dysregulated expression of adipokines in white adipose tissue, Int J Endocrinol, 2013, 801743, 10.1155/2013/801743

Zachwieja, 1997, Voluntary wheel running decreases adipose tissue mass and expression of leptin mRNA in osborne-mendel rats, Diabetes, 46, 1159, 10.2337/diabetes.46.7.1159

Berggren, 2005, Fat as an endocrine organ: influence of exercise, J Appl Physiol., 99, 757, 10.1152/japplphysiol.00134.2005

Halle, 1999, Concurrent reductions of serum leptin and lipids during weight loss in obese men with type ii diabetes, Am J Physiol, 277, E277, 10.1152/ajpendo.1999.277.2.E277

Miyatake, 2004, Changes in serum leptin concentrations in overweight japanese men after exercise, Diabetes Obes Metab, 6, 332, 10.1111/j.1462-8902.2004.00351.x

Polak, 2006, Effect of aerobic training on plasma levels and subcutaneous abdominal adipose tissue gene expression of adiponectin, leptin, interleukin 6, and tumor necrosis factor alpha in obese women, Metabolism, 55, 1375, 10.1016/j.metabol.2006.06.008

Hulver, 2002, Adiponectin is not altered with exercise training despite enhanced insulin action, Am J Physiol Endocrinol Metab, 283, E861, 10.1152/ajpendo.00150.2002

Boudou, 2003, Absence of exercise-induced variations in adiponectin levels despite decreased abdominal adiposity and improved insulin sensitivity in type 2 diabetic men, Eur J Endocrinol, 149, 421, 10.1530/eje.0.1490421

O'Leary, 2006, Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat, J Appl Physiol., 100, 1584, 10.1152/japplphysiol.01336.2005

Kondo, 2006, Effect of exercise on circulating adipokine levels in obese young women, Endocr J, 53, 189, 10.1507/endocrj.53.189

Fatouros, 2005, Leptin and adiponectin responses in overweight inactive elderly following resistance training and detraining are intensity related, J Clin Endocrinol Metab, 90, 5970, 10.1210/jc.2005-0261

Blüher, 2006, Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: associations with metabolic parameters and insulin resistance and regulation by physical training, J Clin Endocrinol Metab, 91, 2310, 10.1210/jc.2005-2556

Christiansen, 2010, Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: a 12-week randomized intervention study, Am J Physiol Endocrinol Metab, 298, E824, 10.1152/ajpendo.00574.2009

Bruun, 2006, Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects, Am J Physiol Endocrinol Metab, 290, E961, 10.1152/ajpendo.00506.2005

Miyazaki, 2010, Effect of exercise training on adipocyte-size-dependent expression of leptin and adiponectin, Life Sci, 86, 691, 10.1016/j.lfs.2010.03.004

García-Hermoso, 2017, Exercise, adipokines and pediatric obesity: a meta-analysis of randomized controlled trials, Int J Obes, 41, 475, 10.1038/ijo.2016.230

Yang, 2011, Effects of a three-month combined exercise programme on fibroblast growth factor 21 and fetuin-a levels and arterial stiffness in obese women, Clin Endocrinol, 75, 464, 10.1111/j.1365-2265.2011.04078.x

Yang, 2019, Exercise ameliorates the fgf21-adiponectin axis impairment in diet-induced obese mice, Endocr Connect, 8, 596, 10.1530/EC-19-0034

Stanford, 2015, A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis, Diabetes, 64, 2002, 10.2337/db14-0704

Sutherl, 2009, Exercise and adrenaline increase pgc-1{alpha} mRNA expression in rat adipose tissue, J Physiol, 587, 1607, 10.1113/jphysiol.2008.165464

Trevellin, 2014, Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through enos-dependent mechanisms, Diabetes, 63, 2800, 10.2337/db13-1234

De Matteis, 2013, Exercise as a new physiological stimulus for brown adipose tissue activity, Nutr Metab Cardiovasc Dis, 23, 582, 10.1016/j.numecd.2012.01.013

Stinkens, 2018, Exercise training-induced effects on the abdominal subcutaneous adipose tissue phenotype in humans with obesity, J Appl Physiol., 125, 1585, 10.1152/japplphysiol.00496.2018

Vosselman, 2015, Low brown adipose tissue activity in endurance-trained compared with lean sedentary men, Int J Obes (Lond), 39, 1696, 10.1038/ijo.2015.130

Otero-Díaz, 2018, Exercise induces white adipose tissue browning across the weight spectrum in humans, Front Physiol, 9, 1781, 10.3389/fphys.2018.01781

Dewal, 2019, Effects of exercise on brown and beige adipocytes, Biochim Biophys Acta Mol Cell Biol Lipids, 1864, 71, 10.1016/j.bbalip.2018.04.013

Forsythe, 2008, Obesity and inflammation: the effects of weight loss, Nutr Res Rev, 21, 117, 10.1017/S0954422408138732

Selvin, 2007, The effect of weight loss on c-reactive protein: a systematic review, Arch Intern Med, 167, 31, 10.1001/archinte.167.1.31

Heilbronn, 2001, Energy restriction and weight loss on very-low-fat diets reduce c-reactive protein concentrations in obese, healthy women, Arterioscler Thromb Vasc Biol, 21, 968, 10.1161/01.ATV.21.6.968

Madsen, 2008, Weight loss larger than 10% is needed for general improvement of levels of circulating adiponectin and markers of inflammation in obese subjects: a 3-year weight loss study, Eur J Endocrinol, 158, 179, 10.1530/EJE-07-0721

Ellsworth, 2015, Importance of substantial weight loss for altering gene expression during cardiovascular lifestyle modification, Obesity, 23, 1312, 10.1002/oby.21079

You, 2013, Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms, Sports Med, 43, 243, 10.1007/s40279-013-0023-3

Giugliano, 2004, Effect of liposuction on insulin resistance and vascular inflammatory markers in obese women, Br J Plast Surg, 57, 190, 10.1016/j.bjps.2003.12.010

Gabriely, 2002, Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process?, Diabetes, 51, 2951, 10.2337/diabetes.51.10.2951

Illán-Gómez, 2012, Obesity and inflammation: change in adiponectin, C-reactive protein, tumour necrosis factor-alpha and interleukin-6 after bariatric surgery, Obes Surg, 22, 950, 10.1007/s11695-012-0643-y

Moschen, 2010, Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor alpha expression, Gut, 59, 1259, 10.1136/gut.2010.214577

Cancello, 2005, Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss, Diabetes, 54, 2277, 10.2337/diabetes.54.8.2277

Trachta, 2014, Laparoscopic sleeve gastrectomy ameliorates mRNA expression of inflammation-related genes in subcutaneous adipose tissue but not in peripheral monocytes of obese patients, Mol Cell Endocrinol, 383, 96, 10.1016/j.mce.2013.11.013

Hagman, 2017, The short-term and long-term effects of bariatric/metabolic surgery on subcutaneous adipose tissue inflammation in humans, Metabolism, 70, 12, 10.1016/j.metabol.2017.01.030

Kratz, 2016, Improvements in glycemic control after gastric bypass occur despite persistent adipose tissue inflammation, Obesity, 24, 1438, 10.1002/oby.21524

Šrámková, 2016, Comparison of early (2 days) and later (28 days) response of adipose tissue to very low-calorie diet in obese women, J Clin Endocrinol Metab, 101, 5021, 10.1210/jc.2016-2161

Magkos, 2016, Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity, Cell Metab, 23, 591, 10.1016/j.cmet.2016.02.005

Wernstedt Asterholm, 2014, Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling, Cell Metab, 20, 103, 10.1016/j.cmet.2014.05.005

Maruthur, 2016, Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis, Ann Intern Med, 164, 740, 10.7326/M15-2650

Rena, 2013, Molecular mechanism of action of metformin: old or new insights?, Diabetologia, 56, 1898, 10.1007/s00125-013-2991-0

Rena, 2017, The mechanisms of action of metformin, Diabetologia, 60, 1577, 10.1007/s00125-017-4342-z

Yerevanian, 2019, Metformin: mechanisms in human obesity and weight loss, Curr Obes Rep, 8, 156, 10.1007/s13679-019-00335-3

Stumvoll, 1995, Metabolic effects of metformin in non-insulin-dependent diabetes mellitus, N Engl J Med, 333, 550, 10.1056/NEJM199508313330903

Aghili, 2014, Body composition in adults with newly diagnosed type 2 diabetes: effects of metformin, J Diabetes Metab Disord, 13, 88, 10.1186/s40200-014-0088-z

Feng, 2019, Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non-alcoholic fatty liver disease: a randomized trial, J Diabetes Investig, 10, 399, 10.1111/jdi.12888

Kim, 2013, Central administration of metformin into the third ventricle of c57bl/6 mice decreases meal size and number and activates hypothalamic s6 kinase, Am J Physiol Regul Integr Comp Physiol, 305, R499, 10.1152/ajpregu.00099.2013

Helvaci, 2008, Metformin and parameters of physical health, Intern Med, 47, 697, 10.2169/internalmedicine.47.0787

Lee, 1996, Metformin in noninsulin-dependent diabetes mellitus, Pharmacotherapy, 16, 327, 10.1002/j.1875-9114.1996.tb02964.x

Tokubuchi, 2017, Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats, PLoS ONE, 12, e0171293, 10.1371/journal.pone.0171293

Geerling, 2014, Metformin lowers plasma triglycerides by promoting vldl-triglyceride clearance by brown adipose tissue in mice, Diabetes, 63, 880, 10.2337/db13-0194

Watanabe, 2017, Adipose tissue-derived omentin-1 function and regulation, Compr Physiol, 7, 765, 10.1002/cphy.c160043

Lin, 2017, Metformin improves nonalcoholic fatty liver disease in obese mice via down-regulation of apolipoprotein a5 as part of the ampk/lxrα signaling pathway, Oncotarget, 8, 108802, 10.18632/oncotarget.22163

Zhu, 2018, Metformin attenuates triglyceride accumulation in hepg2 cells through decreasing stearyl-coenzyme a desaturase 1 expression, Lipids Health Dis, 17, 114, 10.1186/s12944-018-0762-0

Fung, 2015, Effect of metformin monotherapy on cardiovascular diseases and mortality: a retrospective cohort study on Chinese type 2 diabetes mellitus patients, Cardiovasc Diabetol, 14, 137, 10.1186/s12933-015-0304-2

Griffin, 2017, Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes, Diabetologia, 60, 1620, 10.1007/s00125-017-4337-9

Salpeter, 2008, Meta-analysis: metformin treatment in persons at risk for diabetes mellitus, Am J Med, 121, 149, 10.1016/j.amjmed.2007.09.016

Adeshirlarijaney, 2019, Amelioration of metabolic syndrome by metformin associates with reduced indices of low-grade inflammation independently of the gut microbiota, Am J Physiol Endocrinol Metab, 317, E1121, 10.1152/ajpendo.00245.2019

Saisho, 2015, Metformin and inflammation: its potential beyond glucose-lowering effect, Endocr Metab Immune Disord Drug Targets, 15, 196, 10.2174/1871530315666150316124019

Li, 2009, Metformin inhibits nuclear factor kappab activation and decreases serum high-sensitivity c-reactive protein level in experimental atherogenesis of rabbits, Heart Vessels, 24, 446, 10.1007/s00380-008-1137-7

Ruggiero-Lopez, 1999, Reaction of metformin with dicarbonyl compounds. Possible implication in the inhibition of advanced glycation end product formation, Biochem Pharmacol, 58, 1765, 10.1016/S0006-2952(99)00263-4

Beisswenger, 2003, Metformin inhibition of glycation processes, Diabetes Metab, 29, 6S95, 10.1016/S1262-3636(03)72793-1

Burmeister, 2017, The hypothalamic glucagon-like peptide 1 receptor is sufficient but not necessary for the regulation of energy balance and glucose homeostasis in mice, Diabetes, 66, 372, 10.2337/db16-1102

López-Ferreras, 2018, Lateral hypothalamic glp-1 receptors are critical for the control of food reinforcement, ingestive behavior and body weight, Mol Psychiatry, 23, 1157, 10.1038/mp.2017.187

Garber, 2011, Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes, Diabetes Obes Metab, 13, 348, 10.1111/j.1463-1326.2010.01356.x

Nauck, 2013, Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the lead-2 study, Diabetes Obes Metab, 15, 204, 10.1111/dom.12012

Nauck, 2009, Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the lead (liraglutide effect and action in diabetes)-2 study, Diabetes Care, 32, 84, 10.2337/dc08-1355

Jendle, 2009, Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue, Diabetes Obes Metab, 11, 1163, 10.1111/j.1463-1326.2009.01158.x

Inoue, 2011, Short-term effects of liraglutide on visceral fat adiposity, appetite, and food preference: a pilot study of obese japanese patients with type 2 diabetes, Cardiovasc Diabetol, 10, 109, 10.1186/1475-2840-10-109

Hansotia, 2007, Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure, J Clin Invest, 117, 143, 10.1172/JCI25483

Kim Chung, 2009, Exendin-4, a glp-1 receptor agonist, directly induces adiponectin expression through protein kinase a pathway and prevents inflammatory adipokine expression, Biochem Biophys Res Commun, 390, 613, 10.1016/j.bbrc.2009.10.015

Ejarque, 2019, Role of adipose tissue glp-1r expression in metabolic improvement after bariatric surgery in patients with type 2 diabetes, Sci Rep, 9, 6274, 10.1038/s41598-019-42770-1

Marso, 2016, Liraglutide and cardiovascular outcomes in type 2 diabetes, N Engl J Med, 375, 311, 10.1056/NEJMoa1603827

Ansar, 2011, Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: focus on incretins, Cardiovasc Diabetol, 10, 61, 10.1186/1475-2840-10-61

Arakawa, 2010, Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4, Diabetes, 59, 1030, 10.2337/db09-1694

Gaspari, 2011, A glp-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an apoe-/- mouse model, Diab Vasc Dis Res, 8, 117, 10.1177/1479164111404257

Iacobellis, 2017, Liraglutide causes large and rapid epicardial fat reduction, Obesity, 25, 311, 10.1002/oby.21718

Gallo, 2015, Probing sglt2 as a therapeutic target for diabetes: basic physiology and consequences, Diab Vasc Dis Res, 12, 78, 10.1177/1479164114561992

Neal, 2017, Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med, 377, 644, 10.1056/NEJMoa1611925

Chilton, 2015, Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes, Diabetes Obes Metab, 17, 1180, 10.1111/dom.12572

Tikkanen, 2015, Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension, Diabetes Care, 38, 420, 10.2337/dc14-1096

Tahara, 2013, Effects of sglt2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice, Eur J Pharmacol, 715, 246, 10.1016/j.ejphar.2013.05.014

Honda, 2016, The selective sglt2 inhibitor ipragliflozin has a therapeutic effect on nonalcoholic steatohepatitis in mice, PLoS ONE, 11, e0146337, 10.1371/journal.pone.0146337

Qiang, 2015, Treatment with the sglt2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus, Diabetol Metab Syndr, 7, 104, 10.1186/s13098-015-0102-8

Osataphan, 2019, Sglt2 inhibition reprograms systemic metabolism via fgf21-dependent and -independent mechanisms, JCI Insight, 4, 1, 10.1172/jci.insight.123130

Kuchay, 2018, Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (e-lift trial), Diabetes Care, 41, 1801, 10.2337/dc18-0165

Häring, 2013, Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial, Diabetes Care, 36, 3396, 10.2337/dc12-2673

Kovacs, 2014, Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: A 24-week, randomized, placebo-controlled trial, Diabetes Obes Metab, 16, 147, 10.1111/dom.12188

Rosenstock, 2014, Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes, Diabetes Care, 37, 1815, 10.2337/dc13-3055

Xu, 2017, Sglt2 inhibition by empagliflozin promotes fat utilization and browning and attenuates inflammation and insulin resistance by polarizing m2 macrophages in diet-induced obese mice, EBiomedicine, 20, 137, 10.1016/j.ebiom.2017.05.028

Obata, 2016, Tofogliflozin improves insulin resistance in skeletal muscle and accelerates lipolysis in adipose tissue in male mice, Endocrinology, 157, 1029, 10.1210/en.2015-1588

Angrisani, 2015, Bariatric surgery worldwide 2013, Obes Surg., 25, 1822, 10.1007/s11695-015-1657-z

Galanakis, 2015, Computed tomography-based assessment of abdominal adiposity changes and their impact on metabolic alterations following bariatric surgery, World J Surg, 39, 417, 10.1007/s00268-014-2826-2

Keidar, 2014, Baseline abdominal lipid partitioning is associated with the metabolic response to bariatric surgery, Obes Surg, 24, 1709, 10.1007/s11695-014-1249-3

Faria, 2014, Metabolic score: insights on the development and prediction of remission of metabolic syndrome after gastric bypass, Ann Surg, 260, 279, 10.1097/SLA.0000000000000686

Toro-Ramos, 2015, Continued loss in visceral and intermuscular adipose tissue in weight-stable women following bariatric surgery, Obesity, 23, 62, 10.1002/oby.20932

Yoon, 2007, Changes in the abdominal fat distribution after gastrectomy: computed tomography assessment, ANZ J Surg, 77, 121, 10.1111/j.1445-2197.2006.03990.x

Kim, 2014, Effects of bariatric surgery on metabolic and nutritional parameters in severely obese Korean patients with type 2 diabetes: a prospective 2-year follow up, J Diabetes Investig, 5, 221, 10.1111/jdi.12137

Singh, 2017, Ectopic fat accumulation in the pancreas and its clinical relevance: a systematic review, meta-analysis, and meta-regression, Metabolism, 69, 1, 10.1016/j.metabol.2016.12.012

Gaborit, 2015, Ectopic fat storage in the pancreas using 1h-mrs: importance of diabetic status and modulation with bariatric surgery-induced weight loss, Int J Obes, 39, 480, 10.1038/ijo.2014.126

Cancello, 2013, Permanence of molecular features of obesity in subcutaneous adipose tissue of ex-obese subjects, Int J Obes, 37, 867, 10.1038/ijo.2013.7

Andersson, 2014, Changes in subcutaneous fat cell volume and insulin sensitivity after weight loss, Diabetes Care, 37, 1831, 10.2337/dc13-2395

Chen, 2012, Serum leptin levels are inversely correlated with omental gene expression of adiponectin and markedly decreased after gastric bypass surgery, Surg Endosc, 26, 1476, 10.1007/s00464-011-2059-5

Auguet, 2014, Clinical and adipocytokine changes after bariatric surgery in morbidly obese women, Obesity, 22, 188, 10.1002/oby.20470

Sams, 2016, Effect of bariatric surgery on systemic and adipose tissue inflammation, Surg Endosc, 30, 3499, 10.1007/s00464-015-4638-3

Miller, 2011, Serial changes in inflammatory biomarkers after roux-en-y gastric bypass surgery, Surg Obes Relat Dis, 7, 618, 10.1016/j.soard.2011.03.006

Aghamohammadzadeh, 2013, Effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity, J Am Coll Cardiol, 62, 128, 10.1016/S0140-6736(13)60458-4

Emery, 2007, Gastric bypass surgery is associated with reduced inflammation and less depression: a preliminary investigation, Obes Surg, 17, 759, 10.1007/s11695-007-9140-0

Gumbau, 2014, A prospective study on inflammatory parameters in obese patients after sleeve gastrectomy, Obes Surg, 24, 903, 10.1007/s11695-014-1186-1

Holdstock, 2005, Crp reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects, Int J Obes, 29, 1275, 10.1038/sj.ijo.0803000

Iannelli, 2009, Impact of laparoscopic roux-en-y gastric bypass on metabolic syndrome, inflammation, and insulin resistance in super versus morbidly obese women, Obes Surg, 19, 577, 10.1007/s11695-008-9764-8

Iannelli, 2014, Body composition, anthropometrics, energy expenditure, systemic inflammation, in premenopausal women 1 year after laparoscopic roux-en-y gastric bypass, Surg Endosc, 28, 500, 10.1007/s00464-013-3191-1

Monte, 2012, Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after roux-en-y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitus, Surgery, 151, 587, 10.1016/j.surg.2011.09.038

Viardot, 2010, The effects of weight loss and gastric banding on the innate and adaptive immune system in type 2 diabetes and prediabetes, J Clin Endocrinol Metab, 95, 2845, 10.1210/jc.2009-2371

Aron-Wisnewsky, 2009, Human adipose tissue macrophages: M1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss, J Clin Endocrinol Metab, 94, 4619, 10.1210/jc.2009-0925

Pardina, 2012, Only c-reactive protein, but not tnf-α or il6, reflects the improvement in inflammation after bariatric surgery, Obes Surg, 22, 131, 10.1007/s11695-011-0546-3

Lips, 2014, Calorie restriction and roux-en-y gastric bypass have opposing effects on circulating fgf21 in morbidly obese subjects, Clin Endocrinol, 81, 862, 10.1111/cen.12496

Jansen, 2011, Alterations of hormonally active fibroblast growth factors after roux-en-y gastric bypass surgery, Dig Dis, 29, 48, 10.1159/000324128

Pei, 2018, Sleeve gastrectomy attenuates high fat diet-induced non-alcoholic fatty liver disease, Lipids Health Dis, 17, 243, 10.1186/s12944-018-0875-5

Gómez-Ambrosi, 2017, Fgf19 and fgf21 serum concentrations in human obesity and type 2 diabetes behave differently after diet- or surgically-induced weight loss, Clin Nutr, 36, 861, 10.1016/j.clnu.2016.04.027

Haluzíková, 2013, Laparoscopic sleeve gastrectomy differentially affects serum concentrations of fgf-19 and fgf-21 in morbidly obese subjects, Obesity, 21, 1335, 10.1002/oby.20208

Angelin, 2012, Circulating fibroblast growth factors as metabolic regulators–a critical appraisal, Cell Metab, 16, 693, 10.1016/j.cmet.2012.11.001

Sheng, 2017, The long-term effects of bariatric surgery on type 2 diabetes remission, microvascular and macrovascular complications, and mortality: a systematic review and meta-analysis, Obes Surg, 27, 2724, 10.1007/s11695-017-2866-4

Sjöström, 2014, Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications, JAMA, 311, 2297, 10.1001/jama.2014.5988

Sjöström, 2013, Review of the key results from the Swedish obese subjects (sos) trial - a prospective controlled intervention study of bariatric surgery, J Intern Med, 273, 219, 10.1111/joim.12012

Sjöström, 2004, Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery, N Engl J Med, 351, 2683, 10.1056/NEJMoa035622

Diamant, 2003, Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence, Drugs, 63, 1373, 10.2165/00003495-200363130-00004

Day, 1999, Thiazolidinediones: a new class of antidiabetic drugs, Diabet Med, 16, 179, 10.1046/j.1464-5491.1999.00023.x

Mauvais-Jarvis, 2001, Therapeutic perspectives for type 2 diabetes mellitus: molecular and clinical insights, Diabetes Metab, 27, 415

Fonseca, 2003, Effect of thiazolidinediones on body weight in patients with diabetes mellitus, Am J Med, 115, 42S, 10.1016/j.amjmed.2003.09.005

Adams, 1997, Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation, J Clin Invest, 100, 3149, 10.1172/JCI119870

Nichols, 2007, Weight changes following the initiation of new anti-hyperglycaemic therapies, Diabetes Obes Metab, 9, 96, 10.1111/j.1463-1326.2006.00580.x

Boden, 2006, Recent findings concerning thiazolidinediones in the treatment of diabetes, Expert Opin Investig Drugs, 15, 243, 10.1517/13543784.15.3.243

Maeda, 2001, PPARγ ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein, Diabetes, 50, 2094, 10.2337/diabetes.50.9.2094

Pellegrinelli, 2016, Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues, Diabetologia, 59, 1075, 10.1007/s00125-016-3933-4

Miyazaki, 2002, Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients, J Clin Endocrinol Metab, 87, 2784, 10.1210/jcem.87.6.8567

Dietze-Schroeder, 2005, Autocrine action of adiponectin on human fat cells prevents the release of insulin resistance-inducing factors, Diabetes, 54, 2003, 10.2337/diabetes.54.7.2003

Zoico, 2009, The effects of adiponectin on interleukin-6 and mcp-1 secretion in lipopolysaccharide-treated 3t3-l1 adipocytes: role of the nf-kappab pathway, Int J Mol Med, 24, 847, 10.3892/ijmm_00000302

Fasshauer, 2003, Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3t3-l1 adipocytes, Biochem Biophys Res Commun, 301, 1045, 10.1016/S0006-291X(03)00090-1

Kappes, 2000, Influences of ionomycin, dibutyryl-cycloamp and tumour necrosis factor-alpha on intracellular amount and secretion of apm1 in differentiating primary human preadipocytes, Horm Metab Res, 32, 548, 10.1055/s-2007-978684

Goldberg, 2005, A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia, Diabetes Care, 28, 1547, 10.2337/diacare.28.7.1547

Erdmann, 2009, Thiazolidinediones and cardiovascular risk - a question of balance, Curr Cardiol Rev, 5, 155, 10.2174/157340309788970333

van Wijk, 2003, Thiazolidinediones and blood lipids in type 2 diabetes, Arterioscler Thromb Vasc Biol, 23, 1744, 10.1161/01.ATV.0000090521.25968.4D

Dormandy, 2005, Secondary prevention of macrovascular events in patients with type 2 diabetes in the proactive study (prospective pioglitazone clinical trial in macrovascular events): a randomised controlled trial, Lancet, 366, 1279, 10.1016/S0140-6736(05)67528-9

Ridker, 2017, Antiinflammatory therapy with canakinumab for atherosclerotic disease, N Engl J Med, 377, 1119, 10.1056/NEJMoa1707914

Tardif, 2019, Efficacy and safety of low-dose colchicine after myocardial infarction, N Engl J Med, 381, 2497, 10.1056/NEJMoa1912388

Blanco-Colio, 2003, Anti-inflammatory and immunomodulatory effects of statins, Kidney Int, 63, 12, 10.1046/j.1523-1755.2003.00744.x

Zeiser, 2018, Immune modulatory effects of statins, Immunology, 154, 69, 10.1111/imm.12902

Jialal, 2001, Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive c-reactive protein levels, Circulation, 103, 1933, 10.1161/01.CIR.103.15.1933

Shovman, 2002, Antiinflammatory and immunomodulatory properties of statins, Immunol Res, 25, 271, 10.1385/IR:25:3:271

Baigent, 2005, Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins, Lancet, 366, 1267, 10.1016/S0140-6736(05)67394-1

Baigent, 2010, Efficacy and safety of more intensive lowering of ldl cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials, Lancet, 376, 1670, 10.1016/S0140-6736(10)61350-5

Soucek, 2015, Effects of atorvastatin (80 mg) therapy on quantity of epicardial adipose tissue in patients undergoing pulmonary vein isolation for atrial fibrillation, Am J Cardiol, 116, 1443, 10.1016/j.amjcard.2015.07.067

Takei, 2019, Myeloid hmg-coa (3-hydroxy-3-methylglutaryl-coenzyme a) reductase determines adipose tissue inflammation, insulin resistance and hepatic steatosis in diet-induced obese mice, Diabetes, 69, 158, 10.2337/db19-0076

Turnbaugh, 2008, Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome, Cell Host Microbe, 3, 213, 10.1016/j.chom.2008.02.015

Ley, 2006, Microbial ecology: human gut microbes associated with obesity, Nature, 444, 1022, 10.1038/4441022a

Drissi, 2016, Metabolic role of lactobacilli in weight modification in humans and animals, Microb Pathog, 106, 182, 10.1016/j.micpath.2016.03.006

Patil, 2012, Molecular analysis of gut microbiota in obesity among indian individuals, J Biosci, 37, 647, 10.1007/s12038-012-9244-0

Liu, 2017, Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention, Nat Med, 23, 859, 10.1038/nm.4358

Bik, 2015, You lose some, you win some: weight loss induces microbiota and metabolite shifts, EBioMedicine, 2, 806, 10.1016/j.ebiom.2015.07.037

Damms-Machado, 2015, Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption, Biomed Res Int, 2015, 806248, 10.1155/2015/806248

Bäckhed, 2004, The gut microbiota as an environmental factor that regulates fat storage, Proc Natl Acad Sci USA, 101, 15718, 10.1073/pnas.0407076101

Bäckhed, 2007, Mechanisms underlying the resistance to diet-induced obesity in germ-free mice, Proc Natl Acad Sci USA, 104, 979, 10.1073/pnas.0605374104

Turnbaugh, 2006, An obesity-associated gut microbiome with increased capacity for energy harvest, Nature, 444, 1027, 10.1038/nature05414

Cani, 2012, Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity, Gut Microbes, 3, 279, 10.4161/gmic.19625

Lau, 2017, Bridging the gap between gut microbial dysbiosis and cardiovascular diseases, Nutrients, 9, 1, 10.3390/nu9080859

Cani, 2008, Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice, Diabetes, 57, 1470, 10.2337/db07-1403

Moreira, 2012, Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia, Br J Nutr, 108, 801, 10.1017/S0007114512001213

de La Serre, 2010, Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation, Am J Physiol Gastrointest Liver Physiol, 299, G440, 10.1152/ajpgi.00098.2010

Cani, 2007, Metabolic endotoxemia initiates obesity and insulin resistance, Diabetes, 56, 1761, 10.2337/db06-1491

Lassenius, 2011, Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation, Diabetes Care, 34, 1809, 10.2337/dc10-2197

Brun, 2007, Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis, Am J Physiol Gastrointest Liver Physiol, 292, G518, 10.1152/ajpgi.00024.2006

Jiao, 2018, Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in nafld, Gut, 67, 1881, 10.1136/gutjnl-2017-314307

Pierre, 2016, Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice, Am J Physiol Gastrointest Liver Physiol, 311, G286, 10.1152/ajpgi.00202.2016

Koren, 2011, Human oral, gut, and plaque microbiota in patients with atherosclerosis, Proc Natl Acad Sci USA, 108, 4592, 10.1073/pnas.1011383107

Ridlon, 2014, Bile acids and the gut microbiome, Curr Opin Gastroenterol, 30, 332, 10.1097/MOG.0000000000000057

Schaap, 2014, Bile acid receptors as targets for drug development, Nat Rev Gastroenterol Hepatol, 11, 55, 10.1038/nrgastro.2013.151

Cornejo-Pareja, 2019, Importance of gut microbiota in obesity, Eur J Clin Nutr, 72, 26, 10.1038/s41430-018-0306-8

Russell, 2003, The enzymes, regulation, and genetics of bile acid synthesis, Annu Rev Biochem, 72, 137, 10.1146/annurev.biochem.72.121801.161712

Cariou, 2011, Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults, Nutr Metab, 8, 48, 10.1186/1743-7075-8-48

Svensson, 2013, The tgr5 gene is expressed in human subcutaneous adipose tissue and is associated with obesity, weight loss and resting metabolic rate, Biochem Biophys Res Commun, 433, 563, 10.1016/j.bbrc.2013.03.031

Watanabe, 2006, Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation, Nature, 439, 484, 10.1038/nature04330

Cariou, 2006, The farnesoid x receptor modulates adiposity and peripheral insulin sensitivity in mice, J Biol Chem, 281, 11039, 10.1074/jbc.M510258200

Frikke-Schmidt, 2016, Does bariatric surgery improve adipose tissue function?, Obes Rev, 17, 795, 10.1111/obr.12429

Keitel, 2008, Expression and function of the bile acid receptor tgr5 in kupffer cells, Biochem Biophys Res Commun, 372, 78, 10.1016/j.bbrc.2008.04.171

Lou, 2014, Gpbar1/tgr5 mediates bile acid-induced cytokine expression in murine kupffer cells, PLoS ONE, 9, e93567, 10.1371/journal.pone.0093567

Wang, 2008, Farnesoid x receptor antagonizes nuclear factor kappab in hepatic inflammatory response, Hepatology, 48, 1632, 10.1002/hep.22519

De Giorgi, 2015, Long-term effects of roux-en-y gastric bypass on postprandial plasma lipid and bile acids kinetics in female non diabetic subjects: a cross-sectional pilot study, Clin Nutr, 34, 911, 10.1016/j.clnu.2014.09.018

Kohli, 2015, Bile acid signaling: mechanism for bariatric surgery, cure for nash?, Dig Dis, 33, 440, 10.1159/000371699

Albaugh, 2015, Early increases in bile acids post roux-en-y gastric bypass are driven by insulin-sensitizing, secondary bile acids, J Clin Endocrinol Metab, 100, E1225, 10.1210/jc.2015-2467

Ryan, 2014, Fxr is a molecular target for the effects of vertical sleeve gastrectomy, Nature, 509, 183, 10.1038/nature13135

Rizzo, 2006, The farnesoid x receptor promotes adipocyte differentiation and regulates adipose cell function in vivo, Mol Pharmacol, 70, 1164, 10.1124/mol.106.023820

Abdelkarim, 2010, The farnesoid x receptor regulates adipocyte differentiation and function by promoting peroxisome proliferator-activated receptor-gamma and interfering with the wnt/beta-catenin pathways, J Biol Chem, 285, 36759, 10.1074/jbc.M110.166231

Qin, 2012, A metagenome-wide association study of gut microbiota in type 2 diabetes, Nature, 490, 55, 10.1038/nature11450

Burcelin, 2016, Gut microbiota and immune crosstalk in metabolic disease, Mol Metab, 5, 771, 10.1016/j.molmet.2016.05.016

Zhao, 2018, Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes, Science, 359, 1151, 10.1126/science.aao5774

Chan, 2016, High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma a-fabp and cholesterol: a pilot study of high fat diet and its intervention with lactobacillus rhamnosus gg (lgg) or telmisartan in apoe-/- mice, BMC Microbiol, 16, 264, 10.1186/s12866-016-0883-4

Gao, 2009, Butyrate improves insulin sensitivity and increases energy expenditure in mice, Diabetes, 58, 1509, 10.2337/db08-1637

Kimura, 2013, The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor gpr43, Nat Commun, 4, 1829, 10.1038/ncomms2852

Tang, 2017, The gut microbiome and its role in cardiovascular diseases, Circulation, 135, 1008, 10.1161/CIRCULATIONAHA.116.024251

Kimura, 2014, The scfa receptor gpr43 and energy metabolism, Front Endocrinol, 5, 85, 10.3389/fendo.2014.00085

Vinolo, 2011, Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils, J Nutr Biochem, 22, 849, 10.1016/j.jnutbio.2010.07.009

Vinolo, 2012, Tributyrin attenuates obesity-associated inflammation and insulin resistance in high-fat-fed mice, Am J Physiol Endocrinol Metab, 303, E272, 10.1152/ajpendo.00053.2012

Kim, 2014, Gut microbiota-derived short-chain fatty acids, t cells, and inflammation, Immune Netw, 14, 277, 10.4110/in.2014.14.6.277

Asarat, 2015, Short-chain fatty acids produced by synbiotic mixtures in skim milk differentially regulate proliferation and cytokine production in peripheral blood mononuclear cells, Int J Food Sci Nutr, 66, 755, 10.3109/09637486.2015.1088935

Fabian, 2006, Influence of daily consumption of probiotic and conventional yoghurt on the plasma lipid profile in young healthy women, Ann Nutr Metab, 50, 387, 10.1159/000094304

Anderson, 1999, Effect of fermented milk (yogurt) containing lactobacillus acidophilus l1 on serum cholesterol in hypercholesterolemic humans, J Am Coll Nutr, 18, 43, 10.1080/07315724.1999.10718826

Pindjakova, 2017, Gut dysbiosis and adaptive immune response in diet-induced obesity vs. Systemic inflammation, Front Microbiol, 8, 1157, 10.3389/fmicb.2017.01157

Clarke, 2014, Minireview: gut microbiota: the neglected endocrine organ, Mol Endocrinol, 28, 1221, 10.1210/me.2014-1108

Thaiss, 2014, The interplay between the innate immune system and the microbiota, Curr Opin Immunol, 26, 41, 10.1016/j.coi.2013.10.016

Kato, 2014, The role of the adaptive immune system in regulation of gut microbiota, Immunol Rev, 260, 67, 10.1111/imr.12185

Honda, 2016, The microbiota in adaptive immune homeostasis and disease, Nature, 535, 75, 10.1038/nature18848

Ohira, 2013, Butyrate attenuates inflammation and lipolysis generated by the interaction of adipocytes and macrophages, J Atheroscler Thromb, 20, 425, 10.5551/jat.15065

Wang, 2015, Sodium butyrate alleviates adipocyte inflammation by inhibiting nlrp3 pathway, Sci Rep, 5, 12676, 10.1038/srep12676

Alemán, 2018, Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women, J Transl Med, 16, 244, 10.1186/s12967-018-1619-z

Janssens, 2003, Role of toll-like receptors in pathogen recognition, Clin Microbiol Rev, 16, 637, 10.1128/CMR.16.4.637-646.2003

Pineiro, 2008, Fao technical meeting on prebiotics, J Clin Gastroenterol, 42, S156, 10.1097/MCG.0b013e31817f184e

Ettinger, 2014, The influence of the human microbiome and probiotics on cardiovascular health, Gut Microbes, 5, 719, 10.4161/19490976.2014.983775

Kim, 2018, Probiotics, prebiotics, synbiotics and insulin sensitivity, Nutr Res Rev, 31, 35, 10.1017/S095442241700018X

Karamali, 2016, Effects of probiotic supplementation on glycaemic control and lipid profiles in gestational diabetes: a randomized, double-blind, placebo-controlled trial, Diabetes Metab, 42, 234, 10.1016/j.diabet.2016.04.009

Crommen, 2017, Microbial regulation of glucose metabolism and insulin resistance, Genes, 9, 1, 10.3390/genes9010010

Yoo, 2013, Probiotics l. Plantarum and l. Curvatus in combination alter hepatic lipid metabolism and suppress diet-induced obesity, Obesity, 21, 2571, 10.1002/oby.20428

Wang, 2015, Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice, ISME J, 9, 1, 10.1038/ismej.2014.99

Everard, 2013, Cross-talk between akkermansia muciniphila and intestinal epithelium controls diet-induced obesity, Proc Natl Acad Sci USA, 110, 9066, 10.1073/pnas.1219451110

Mischke, 2018, Specific synbiotics in early life protect against diet-induced obesity in adult mice, Diabetes Obes Metab, 20, 1408, 10.1111/dom.13240

Aronsson, 2010, Decreased fat storage by Lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein (angptl4), PLoS ONE, 5, e13087, 10.1371/journal.pone.0013087

Park, 2013, Supplementation of Lactobacillus curvatus hy7601 and Lactobacillus plantarum ky1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity, PLoS ONE, 8, e59470, 10.1371/journal.pone.0059470

Ukibe, 2015, Administration of lactobacillus gasseri sbt2055 suppresses macrophage infiltration into adipose tissue in diet-induced obese mice, Br J Nutr, 114, 1180, 10.1017/S0007114515002627

Miyoshi, 2014, Anti-obesity effect of lactobacillus gasseri sbt2055 accompanied by inhibition of pro-inflammatory gene expression in the visceral adipose tissue in diet-induced obese mice, Eur J Nutr, 53, 599, 10.1007/s00394-013-0568-9

Kadooka, 2010, Regulation of abdominal adiposity by probiotics (lactobacillus gasseri sbt2055) in adults with obese tendencies in a randomized controlled trial, Eur J Clin Nutr, 64, 636, 10.1038/ejcn.2010.19

Gibson, 1999, Dietary modulation of the human gut microflora using the prebiotics oligofructose and inulin, J Nutr, 129, 1438S, 10.1093/jn/129.7.1438S

Cicero, 2017, Lipid-lowering nutraceuticals in clinical practice: position paper from an international lipid expert panel, Nutr Rev, 75, 731, 10.1093/nutrit/nux047