Interactions between adipose tissue and the immune system in health and malnutrition

Seminars in Immunology - Tập 27 - Trang 322-333 - 2015
Felix M. Wensveen1,2, Sonja Valentić1, Marko Šestan1, Tamara Turk Wensveen3, Bojan Polić1
1Department of Histology & Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
2Department of Experimental Immunology, Amsterdam Medical Centre, Amsterdam, The Netherlands
3Department of Internal Medicine, University Hospital Rijeka, Rijeka, Croatia

Tài liệu tham khảo

Murray, 2003, Naive T cells are maintained by thymic output in early ages but by proliferation without phenotypic change after age twenty, Immunol. Cell Biol., 81, 487, 10.1046/j.1440-1711.2003.01191.x Gubser, 2013, Rapid effector function of memory CD8(+) T cells requires an immediate-early glycolytic switch, Nature. Immunol., 14, 1064-+, 10.1038/ni.2687 van der Windt, 2012, Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development, Immunity, 36, 68, 10.1016/j.immuni.2011.12.007 Wing, 1988, Acute starvation in mice reduces the number of T cells and suppresses the development of T-cell-mediated immunity, Immunology, 63, 677 Ronti, 2006, The endocrine function of adipose tissue: an update, Clin. Endocrinol. (Oxf.), 64, 355 Ouchi, 2011, Adipokines in inflammation and metabolic disease, Nat. Rev. Immunol., 11, 85, 10.1038/nri2921 Leibel, 2008, Molecular physiology of weight regulation in mice and humans, Int. J. Obes. (Lond), 32, S98, 10.1038/ijo.2008.245 Lord, 1998, Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression, Nature, 394, 897, 10.1038/29795 Popkin, 2009, Global changes in diet and activity patterns as drivers of the nutrition transition, Nestle Nutr. Workshop Ser. Pediatr. Program., 63, 1, 10.1159/000209967 Stevens, 2012, National, regional, and global trends in adult overweight and obesity prevalences, Popul. Health Metr., 10, 22, 10.1186/1478-7954-10-22 Hotamisligil, 2006, Inflammation and metabolic disorders, Nature, 444, 860, 10.1038/nature05485 Kern, 1995, The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase, J. Clin. Invest., 95, 2111, 10.1172/JCI117899 Visser, 1999, Elevated C-reactive protein levels in overweight and obese adults, JAMA, 282, 2131, 10.1001/jama.282.22.2131 Vozarova, 2001, Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion, Obes. Res., 9, 414, 10.1038/oby.2001.54 Weisberg, 2003, Obesity is associated with macrophage accumulation in adipose tissue, J. Clin. Invest., 112, 1796, 10.1172/JCI200319246 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 Johnson, 2012, The inflammation highway: metabolism accelerates inflammatory traffic in obesity, Immunol. Rev., 249, 218, 10.1111/j.1600-065X.2012.01151.x Sanchez-Gurmaches, 2014, Adipocyte lineages: tracing back the origins of fat, Biochim. Biophys. Acta, 1842, 340, 10.1016/j.bbadis.2013.05.027 Banerji, 1999, Body composition, visceral fat, leptin, and insulin resistance in Asian Indian men, J. Clin. Endocrinol. Metab., 84, 137 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 Sluik, 2011, Associations between general and abdominal adiposity and mortality in individuals with diabetes mellitus, Am. J. Epidemiol., 174, 22, 10.1093/aje/kwr048 Guilherme, 2008, Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes, Nat. Rev. Mol. Cell Biol., 9, 367, 10.1038/nrm2391 Betz, 2015, Human Brown adipose tissue: what we have learned so far, Diabetes, 64, 2352, 10.2337/db15-0146 Nedergaard, 2007, Unexpected evidence for active brown adipose tissue in adult humans, Am. J. Physiol. Endocrinol. Metab., 293, E444, 10.1152/ajpendo.00691.2006 Sethi, 2007, Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation, J. Lipid Res., 48, 1253, 10.1194/jlr.R700005-JLR200 Sanchez-Gurmaches, 2014, Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed, Nat. Commun., 5, 4099, 10.1038/ncomms5099 Garvey, 2014, American association of clinical endocrinologists and american college of endocrinology position statement on the 2014 advanced framework for a new diagnosis of obesity as a chronic disease, Endocrinol. Pract., 20, 977, 10.4158/EP14280.PS West, 1992, Dietary obesity in nine inbred mouse strains, Am. J. Physiol., 262, R1025 Wang, 2013, Tracking adipogenesis during white adipose tissue development, expansion and regeneration, Nat. Med., 19, 1338, 10.1038/nm.3324 Jeffery, 2015, Rapid depot-specific activation of adipocyte precursor cells at the onset of obesity, Nat. Cell Biol., 17, 376, 10.1038/ncb3122 Frayn, 1994, Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition, Am. J. Physiol., 266, E308 Horowitz, 1999, Effect of short-term fasting on lipid kinetics in lean and obese women, Am. J. Physiol., 276, E278 Combs, 2001, Endogenous glucose production is inhibited by the adipose-derived protein Acrp30, J. Clin. Invest., 108, 1875, 10.1172/JCI14120 Yamauchi, 2001, The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity, Nat. Med., 7, 941, 10.1038/90984 Maeda, 2002, Diet-induced insulin resistance in mice lacking adiponectin/ACRP30, Nat. Med., 8, 731, 10.1038/nm724 Sada, 2006, Altered levels of adipocytokines in association with insulin resistance in patients with systemic lupus erythematosus, J. Rheumatol., 33, 1545 Balistreri, 2010, The role of adipose tissue and adipokines in obesity-related inflammatory diseases, Mediators Inflamm., 2010, 802078, 10.1155/2010/802078 Leibel, 2002, The role of leptin in the control of body weight, Nutr. Rev., 60, S15, 10.1301/002966402320634788 Despres, 2006, Abdominal obesity and metabolic syndrome, Nature, 444, 881, 10.1038/nature05488 Altintas, 2011, Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice, J. Lipid Res., 52, 480, 10.1194/jlr.M011338 Wensveen, 2015, NK cells link obesity-induced adipose stress to inflammation and insulin resistance, Nat. Immunol., 16, 376, 10.1038/ni.3120 Zhang, 1994, Positional cloning of the mouse obese gene and its human homologue, Nature, 372, 425, 10.1038/372425a0 Bluher, 2015, From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century, Metab.: clin. Exp., 64, 131, 10.1016/j.metabol.2014.10.016 Rayner, 2001, Regulation of leptin production: sympathetic nervous system interactions, J. Mol. Med., 79, 8, 10.1007/s001090100198 Trayhurn, 1982, Effects of overfeeding on energy balance and brown fat thermogenesis in obese (ob/ob) mice, Nature, 295, 323, 10.1038/295323a0 Matarese, 2005, Leptin in immunology, J. Immunol., 174, 3137, 10.4049/jimmunol.174.6.3137 Harris, 2000, Leptin—much more than a satiety signal, Annu. Rev. Nutr., 20, 45, 10.1146/annurev.nutr.20.1.45 Gorska, 2010, Leptin receptors, Eur. J. Med. Res., 15, 50, 10.1186/2047-783X-15-S2-50 Bates, 2003, STAT3 signalling is required for leptin regulation of energy balance but not reproduction, Nature, 421, 856, 10.1038/nature01388 Fruhbeck, 2006, Intracellular signalling pathways activated by leptin, Biochem. J., 393, 7, 10.1042/BJ20051578 Fernandez-Riejos, 2010, Role of leptin in the activation of immune cells, Mediators Inflamm., 2010, 568343, 10.1155/2010/568343 Wisse, 2004, The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity, J. Am. Soc. Nephrol.: JASN, 15, 2792, 10.1097/01.ASN.0000141966.69934.21 Steppan, 2001, The hormone resistin links obesity to diabetes, Nature, 409, 307, 10.1038/35053000 Kusminski, 2005, Role of resistin in obesity, insulin resistance and Type II diabetes, Clin. Sci., 109, 243, 10.1042/CS20050078 Bokarewa, 2005, Resistin, an adipokine with potent proinflammatory properties, J. Immunol., 174, 5789, 10.4049/jimmunol.174.9.5789 Benomar, 2013, Central resistin overexposure induces insulin resistance through Toll-like receptor 4, Diabetes, 62, 102, 10.2337/db12-0237 Kim, 1999, Molecular cloning, expression, and characterization of angiopoietin-related protein. angiopoietin-related protein induces endothelial cell sprouting, J. Biol. Chem., 274, 26523, 10.1074/jbc.274.37.26523 Tabata, 2009, Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance, Cell Metab., 10, 178, 10.1016/j.cmet.2009.08.003 Doi, 2013, Angiopoietin-like protein 2 and risk of type 2 diabetes in a general Japanese population: the Hisayama study, Diabetes care, 36, 98, 10.2337/dc12-0166 Fukuhara, 2005, Visfatin: a protein secreted by visceral fat that mimics the effects of insulin, Science, 307, 426, 10.1126/science.1097243 Adeghate, 2008, Visfatin: structure, function and relation to diabetes mellitus and other dysfunctions, Curr. Med. Chem., 15, 1851, 10.2174/092986708785133004 Samal, 1994, Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor, Mol. Cell Biol., 14, 1431, 10.1128/MCB.14.2.1431 Moschen, 2007, Visfatin, an adipocytokine with proinflammatory and immunomodulating properties, J. Immunol., 178, 1748, 10.4049/jimmunol.178.3.1748 Maeda, 2012, cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript 1), Biochem. Biophys. Res. Commun., 425, 556, 10.1016/j.bbrc.2012.08.023 Schaeffer, 1979, Sensitivity of cultured rat hepatocytes to aflatoxin B1 and benzo(a)pyrene, In Vitro, 15, 437, 10.1007/BF02618412 Yamauchi, 2003, Cloning of adiponectin receptors that mediate antidiabetic metabolic effects, Nature, 423, 762, 10.1038/nature01705 Barnes, 2015, Non-traditional cytokines: how catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system, Cytokine, 72, 210, 10.1016/j.cyto.2015.01.008 Kubota, 2007, Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake, Cell Metab., 6, 55, 10.1016/j.cmet.2007.06.003 Saxena, 2012, Adiponectin deficiency: role in chronic inflammation induced colon cancer, Biochim. Biophys. Acta, 1822, 527, 10.1016/j.bbadis.2011.12.006 Tilg, 2006, Adipocytokines: mediators linking adipose tissue, inflammation and immunity, Nat. Rev. Immunol., 6, 772, 10.1038/nri1937 Wilk, 2011, Adiponectin is a negative regulator of antigen-activated T cells, Eur. J. Immunol., 41, 2323, 10.1002/eji.201041349 White, 1992, Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue, J. Biol. Chem., 267, 9210, 10.1016/S0021-9258(19)50409-4 Lo, 2014, Adipsin is an adipokine that improves beta cell function in diabetes, Cell, 158, 41, 10.1016/j.cell.2014.06.005 Lumeng, 2007, Obesity induces a phenotypic switch in adipose tissue macrophage polarization, J. Clin. Invest., 117, 175, 10.1172/JCI29881 Mosser, 2008, Exploring the full spectrum of macrophage activation, Nat. Rev. Immunol., 8, 958, 10.1038/nri2448 Feuerer, 2009, Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters, Nat. Med., 15, 930, 10.1038/nm.2002 Vasanthakumar, 2015, The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells, Nat. Immunol., 16, 276, 10.1038/ni.3085 Pichery, 2012, Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain, J. Immunol., 188, 3488, 10.4049/jimmunol.1101977 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 Schipper, 2012, Natural killer T cells in adipose tissue prevent insulin resistance, J. Clin. Invest., 122, 3343, 10.1172/JCI62739 Ohmura, 2010, Natural killer T cells are involved in adipose tissues inflammation and glucose intolerance in diet-induced obese mice, Arterioscler. Thromb. Vasc. Biol., 30, 193, 10.1161/ATVBAHA.109.198614 Wu, 2012, Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice, Proc. Natl. Acad. Sci. U S A, 109, E1143, 10.1073/pnas.1200498109 Molofsky, 2013, Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages, J. Exp. Med., 210, 535, 10.1084/jem.20121964 Wu, 2011, Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis, Science, 332, 243, 10.1126/science.1201475 Mauer, 2014, Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin, Nat. Immunol., 15, 423, 10.1038/ni.2865 Brestoff, 2015, Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity, Nature, 519, 242, 10.1038/nature14115 WHO, 2015 Esposito, 2002, Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress, Circulation, 106, 2067, 10.1161/01.CIR.0000034509.14906.AE Ferreira, 2014, Distinct metabolic pathways trigger adipocyte fat accumulation induced by high-carbohydrate and high-fat diets, Nutrition, 30, 1138, 10.1016/j.nut.2014.02.017 El Khoury, 2013, Recent advances in dietary proteins and lipid metabolism, Curr. Opin. Lipid, 24, 207, 10.1097/MOL.0b013e3283613bb7 Jahan-Mihan, 2011, Dietary proteins as determinants of metabolic and physiologic functions of the gastrointestinal tract, Nutrients, 3, 574, 10.3390/nu3050574 Bortolotti, 2009, High protein intake reduces intrahepatocellular lipid deposition in humans, Am. J. Clin. Nutr., 90, 1002, 10.3945/ajcn.2008.27296 Raymond, 2012, Consequences of exchanging carbohydrates for proteins in the cholesterol metabolism of mice fed a high-fat diet, PLoS ONE, 7, e49058, 10.1371/journal.pone.0049058 Hosomi, 2012, Fish protein hydrolysates affect cholesterol metabolism in rats fed non-cholesterol and high-cholesterol diets, J. Med. Food, 15, 299, 10.1089/jmf.2011.1620 Zhang, 1993, Lowering effect of dietary milk-whey protein v. casein on plasma and liver cholesterol concentrations in rats, Br. J. Nutr., 70, 139, 10.1079/BJN19930111 Shukla, 2007, Isoflavone-poor soy protein alters the lipid metabolism of rats by SREBP-mediated down-regulation of hepatic genes, J. Nutr. Biochem., 18, 313, 10.1016/j.jnutbio.2006.05.007 Chen, 2009, Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro, Nutrition, 25, 340, 10.1016/j.nut.2008.08.012 Oliva, 2011, Soya protein ameliorates the metabolic abnormalities of dysfunctional adipose tissue of dyslipidaemic rats fed a sucrose-rich diet, Br. J. Nutr., 105, 1188, 10.1017/S0007114510004915 Sarr, 2011, A high-protein neonatal formula induces a temporary reduction of adiposity and changes later adipocyte physiology, Am. J. Physiol. Regul. Integr. Comp. Physiol., 300, R387, 10.1152/ajpregu.00459.2010 Leidy, 2007, Effects of acute and chronic protein intake on metabolism, appetite, and ghrelin during weight loss, Obesity (Silver Spring), 15, 1215, 10.1038/oby.2007.143 Tovar, 2010, The role of dietary protein on lipotoxicity, Biochim. Biophys. Acta, 1801, 367, 10.1016/j.bbalip.2009.09.007 Mortensen, 2009, Differential effects of protein quality on postprandial lipemia in response to a fat-rich meal in type 2 diabetes: comparison of whey, casein, gluten, and cod protein, Am. J. Clin. Nutr., 90, 41, 10.3945/ajcn.2008.27281 Ceriello, 2004, Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited, Arterioscler. Thromb. Vasc. Biol., 24, 816, 10.1161/01.ATV.0000122852.22604.78 Ott, 2007, Mitochondria, oxidative stress and cell death, Apoptosis, 12, 913, 10.1007/s10495-007-0756-2 Yin, 2012, Mitochondrial thiols in the regulation of cell death pathways, Antioxid. Redox Signal., 17, 1714, 10.1089/ars.2012.4639 Shoelson, 2007, Obesity, inflammation, and insulin resistance, Gastroenterology, 132, 2169, 10.1053/j.gastro.2007.03.059 Xue, 2001, Mechanism of intracellular calcium ([Ca2+]i) inhibition of lipolysis in human adipocytes, FASEB J., 15, 2527, 10.1096/fj.01-0278fje Munoz, 2013, Nutritionally mediated oxidative stress and inflammation, Oxid. Med. Cell Longev., 2013, 610950, 10.1155/2013/610950 Kromhout, 2012, Fish oil and omega-3 fatty acids in cardiovascular disease: do they really work?, Eur. Heart J., 33, 436, 10.1093/eurheartj/ehr362 Rommel, 2007, PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond?, Nat. Rev. Immunol., 7, 191, 10.1038/nri2036 Bellido, 2004, Butter and walnuts, but not olive oil, elicit postprandial activation of nuclear transcription factor kappaB in peripheral blood mononuclear cells from healthy men, Am. J. Clin. Nutr., 80, 1487, 10.1093/ajcn/80.6.1487 Wensveen, 2015, The “Big Bang” in obese fat: events initiating obesity-induced adipose tissue inflammation, Eur. J. Immunol., 45, 2446, 10.1002/eji.201545502 Talukdar, 2012, Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase, Nat. Med., 18, 1407, 10.1038/nm.2885 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 Amano, 2014, Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation, Cell Metab., 19, 162, 10.1016/j.cmet.2013.11.017 Goldszmid, 2012, NK cell-derived interferon-gamma orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection, Immunity, 36, 1047, 10.1016/j.immuni.2012.03.026 Pal, 2012, Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance, Nat. Med., 18, 1279, 10.1038/nm.2851 Pussinen, 2011, Endotoxemia is associated with an increased risk of incident diabetes, Diabetes Care, 34, 392, 10.2337/dc10-1676 Khan, 2009, Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI, Mol. Cell Biol., 29, 1575, 10.1128/MCB.01300-08 Ye, 2007, Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice, Am. J. Physiol. Endocrinol. Metab., 293, E1118, 10.1152/ajpendo.00435.2007 O’Rourke, 2012, Systemic inflammation and insulin sensitivity in obese IFN-gamma knockout mice, Metab. Clin. Exp., 61, 1152, 10.1016/j.metabol.2012.01.018 Nishimura, 2009, CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity, Nat. Med., 15, 914, 10.1038/nm.1964 Winer, 2009, Normalization of obesity-associated insulin resistance through immunotherapy, Nat. Med., 15, 921, 10.1038/nm.2001 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 Li, 2015, LTB4 promotes insulin resistance in obese mice by acting on macrophages, hepatocytes and myocytes, Nat. Med., 21, 239, 10.1038/nm.3800 Vandanmagsar, 2011, The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance, Nat. Med., 17, 179, 10.1038/nm.2279 TUFaAO, 2014 Caulfield, 2004, Undernutrition as an underlying cause of child deaths associated with diarrhea, pneumonia, malaria, and measles, Am. J. Clin. Nutr., 80, 193, 10.1093/ajcn/80.1.193 Hickman, 2014, The effect of malnutrition on norovirus infection, MBio, 5, 10.1128/mBio.01032-13 Neumann, 2004, Child nutrition in developing countries, Pediatr. Ann., 33, 658, 10.3928/0090-4481-20041001-09 Black, 2013, Maternal and child undernutrition and overweight in low-income and middle-income countries, Lancet, 382, 427, 10.1016/S0140-6736(13)60937-X Wang, 2006, The comparative physiology of food deprivation: from feast to famine, Annu. Rev. Physiol., 68, 223, 10.1146/annurev.physiol.68.040104.105739 Cahill, 2006, Fuel metabolism in starvation, Annu. Rev. Nutr., 26, 1, 10.1146/annurev.nutr.26.061505.111258 Hardie, 2014, AMP-activated protein kinase: maintaining energy homeostasis at the cellular and whole-body levels, Annu. Rev. Nutr., 34, 31, 10.1146/annurev-nutr-071812-161148 Fryer, 2002, Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells, Biochem. J., 363, 167, 10.1042/bj3630167 Habets, 2009, Crucial role for LKB1 to AMPKalpha2 axis in the regulation of CD36-mediated long-chain fatty acid uptake into cardiomyocytes, Biochim. Biophys. Acta, 1791, 212, 10.1016/j.bbalip.2008.12.009 Kurth-Kraczek, 1999, 5′ AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle, Diabetes, 48, 1667, 10.2337/diabetes.48.8.1667 Marsin, 2000, Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia, Curr. Biol., 10, 1247, 10.1016/S0960-9822(00)00742-9 Marsin, 2002, The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase, J. Biol. Chem., 277, 30778, 10.1074/jbc.M205213200 Merrill, 1997, AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle, Am. J. Physiol., 273, E1107 Egan, 2011, Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy, Science, 331, 456, 10.1126/science.1196371 Russell, 2013, ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase, Nat. Cell Biol., 15, 741, 10.1038/ncb2757 Bultot, 2012, AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase, Biochem. J., 443, 193, 10.1042/BJ20112026 Gillespie, 1992, Phosphorylation and inactivation of HMG-CoA reductase at the AMP-activated protein kinase site in response to fructose treatment of isolated rat hepatocytes, FEBS Lett., 306, 59, 10.1016/0014-5793(92)80837-7 Jorgensen, 2004, The alpha2-5′AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading, Diabetes, 53, 3074, 10.2337/diabetes.53.12.3074 Koo, 2005, The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism, Nature, 437, 1109, 10.1038/nature03967 Mihaylova, 2011, The AMPK signalling pathway coordinates cell growth, autophagy and metabolism, Nat. Cell Biol., 13, 1016, 10.1038/ncb2329 Claret, 2007, AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons, J. Clin. Invest., 117, 2325, 10.1172/JCI31516 McCrimmon, 2008, Key role for AMP-activated protein kinase in the ventromedial hypothalamus in regulating counterregulatory hormone responses to acute hypoglycemia, Diabetes, 57, 444, 10.2337/db07-0837 Willesen, 1999, Co-localization of growth hormone secretagogue receptor and NPY mRNA in the arcuate nucleus of the rat, Neuroendocrinology, 70, 306, 10.1159/000054491 Yamauchi, 2002, Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase, Nat. Med., 8, 1288, 10.1038/nm788 Cutrera, 2010, Mounting a specific immune response increases energy expenditure of the subterranean rodent Ctenomys talarum (tuco-tuco): implications for intraspecific and interspecific variation in immunological traits, J. Exp. Biol., 213, 715, 10.1242/jeb.037887 Ganeshan, 2014, Metabolic regulation of immune responses, Annu. Rev. Immunol., 32, 609, 10.1146/annurev-immunol-032713-120236 Segal, 2005, How neutrophils kill microbes, Annu. Rev. Immunol., 23, 197, 10.1146/annurev.immunol.23.021704.115653 Boxer, 1977, The effect of 2-deoxyglucose on guinea pig polymorphonuclear leukocyte phagocytosis, J. Cell. Physiol., 91, 89, 10.1002/jcp.1040910110 Sbarra, 1959, The biochemical basis of phagocytosis. I. Metabolic changes during the ingestion of particles by polymorphonuclear leukocytes, J. Biol. Chem., 234, 1355, 10.1016/S0021-9258(18)70011-2 Weisdorf, 1982, Granulocytes utilize different energy sources for movement and phagocytosis, Inflammation, 6, 245, 10.1007/BF00916406 Wynn, 2013, Macrophage biology in development, homeostasis and disease, Nature, 496, 445, 10.1038/nature12034 Vats, 2006, Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation, Cell Metab., 4, 13, 10.1016/j.cmet.2006.05.011 Newsholme, 1986, Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages, Biochem. J., 239, 121, 10.1042/bj2390121 Newsholme, 1989, Rates of utilization of glucose, glutamine and oleate and formation of end-products by mouse peritoneal macrophages in culture, Biochem. J., 261, 211, 10.1042/bj2610211 Cramer, 2003, HIF-1alpha is essential for myeloid cell-mediated inflammation, Cell, 112, 645, 10.1016/S0092-8674(03)00154-5 Frauwirth, 2002, The CD28 signaling pathway regulates glucose metabolism, Immunity, 16, 769, 10.1016/S1074-7613(02)00323-0 Delgoffe, 2009, The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment, Immunity, 30, 832, 10.1016/j.immuni.2009.04.014 Michalek, 2011, Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets, J. Immunol., 186, 3299, 10.4049/jimmunol.1003613 Pearce, 2009, Enhancing CD8 T-cell memory by modulating fatty acid metabolism, Nature, 460, 103, 10.1038/nature08097 Gerriets, 2014, Role of T cells in malnutrition and obesity, Front. Immunol., 5, 379, 10.3389/fimmu.2014.00379 Howard, 1999, Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice, J. Clin. Invest., 104, 1051, 10.1172/JCI6762 Procaccini, 2012, Leptin-induced mTOR activation defines a specific molecular and transcriptional signature controlling CD4+ effector T cell responses, J. Immunol., 189, 2941, 10.4049/jimmunol.1200935 Saucillo, 2014, Leptin metabolically licenses T cells for activation to link nutrition and immunity, J. Immunol., 192, 136, 10.4049/jimmunol.1301158 Tanaka, 2011, Role of central leptin signaling in the starvation-induced alteration of B-cell development, J. Neurosci., 31, 8373, 10.1523/JNEUROSCI.6562-10.2011 Pena-Cruz, 1989, Sendai virus infection of mice with protein malnutrition, J. Virol., 63, 3541, 10.1128/JVI.63.8.3541-3544.1989 Taylor, 2013, Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection in mice, J. Infect. Dis., 207, 501, 10.1093/infdis/jis527 Najera, 2004, Flow cytometry study of lymphocyte subsets in malnourished and well-nourished children with bacterial infections, Clin. Diagn. Lab. Immunol., 11, 577, 10.1128/CDLI.11.3.577-580.2004 Xia, 2014, Anti-CD3 antibody treatment induces hypoglycemia and super tolerance to glucose challenge in mice through enhancing glucose consumption by activated lymphocytes, J. Immunol. Res., 2014, 326708, 10.1155/2014/326708 Jacobs, 2008, Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways, J. Immunol., 180, 4476, 10.4049/jimmunol.180.7.4476 Cham, 2005, Glucose availability regulates IFN-gamma production and p70S6 kinase activation in CD8+ effector T cells, J. Immunol., 174, 4670, 10.4049/jimmunol.174.8.4670 Gonzalez-Torres, 2013, Effect of malnutrition on the expression of cytokines involved in Th1 cell differentiation, Nutrients, 5, 579, 10.3390/nu5020579 Mengheri, 1992, Protein starvation impairs the ability of activated lymphocytes to produce interferon-gamma, J. Interferon Res., 12, 17, 10.1089/jir.1992.12.17 Gonzalez-Martinez, 2008, Expression of cytokine mRNA in lymphocytes of malnourished children, J. Clin. Immunol., 28, 593, 10.1007/s10875-008-9204-5 Murphy, 1979, A Y chromosome associated factor in strain BXSB producing accelerated autoimmunity and lymphoproliferation, Arthritis Rheum., 22, 1188, 10.1002/art.1780221105 Piccio, 2008, Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis, J. Leukoc. Biol., 84, 940, 10.1189/jlb.0208133 Sanna, 2003, Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses, J. Clin. Invest., 111, 241, 10.1172/JCI200316721 Clinthorne, 2013, NK cell maturation and function in C57BL/6 mice are altered by caloric restriction, J. Immunol., 190, 712, 10.4049/jimmunol.1201837 Ritz, 2008, Energy restriction impairs natural killer cell function and increases the severity of influenza infection in young adult male C57BL/6 mice, J. Nutr., 138, 2269, 10.3945/jn.108.093633 Banks, 2000, Activation of downstream signals by the long form of the leptin receptor, J. Biol. Chem., 275, 14563, 10.1074/jbc.275.19.14563 La Cava, 2004, The weight of leptin in immunity, Nat. Rev. Immunol., 4, 371, 10.1038/nri1350 Rodriguez, 2007, Effect of leptin on activation and cytokine synthesis in peripheral blood lymphocytes of malnourished infected children, Clin. Exp. Immunol., 148, 478, 10.1111/j.1365-2249.2007.03361.x Mancuso, 2002, Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia, J. Immunol., 168, 4018, 10.4049/jimmunol.168.8.4018 Dixit, 2003, Leptin induces growth hormone secretion from peripheral blood mononuclear cells via a protein kinase C- and nitric oxide-dependent mechanism, Endocrinology, 144, 5595, 10.1210/en.2003-0600 Caldefie-Chezet, 2001, Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action?, J. Leukoc. Biol., 69, 414, 10.1189/jlb.69.3.414 Caldefie-Chezet, 2003, Leptin regulates functional capacities of polymorphonuclear neutrophils, Free Radical Res., 37, 809, 10.1080/1071576031000097526 Siegmund, 2002, Leptin deficiency, not obesity, protects mice from Con A-induced hepatitis, Eur. J. Immunol., 32, 552, 10.1002/1521-4141(200202)32:2<552::AID-IMMU552>3.0.CO;2-H Tian, 2002, Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation, Biochem. Biophys. Res. Commun., 298, 297, 10.1016/S0006-291X(02)02462-2 Zhao, 2003, Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines, Biochem. Biophys. Res. Commun., 300, 247, 10.1016/S0006-291X(02)02838-3 McGorrian, 2011, Estimating modifiable coronary heart disease risk in multiple regions of the world: the INTERHEART modifiable risk score, Eur. Heart J., 32, 581, 10.1093/eurheartj/ehq448 Wolf, 2014, Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepatitis and liver cancer via cross-talk with hepatocytes, Cancer Cell, 26, 549, 10.1016/j.ccell.2014.09.003 Suganami, 2005, A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha, Arterioscler. Thromb. Vasc. Biol., 25, 2062, 10.1161/01.ATV.0000183883.72263.13 Lopez-Garcia, 2004, Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction, Am. J. Clin. Nutr., 80, 1029, 10.1093/ajcn/80.4.1029 Kabir, 2007, Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study, Am. J. Clin. Nutr., 86, 1670, 10.1093/ajcn/86.6.1670 Kallio, 2007, Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT study, Am. J. Clin. Nutr., 85, 1417, 10.1093/ajcn/85.5.1417 Uusitupa, 2013, Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome—a randomized study (SYSDIET), J. Int. Med., 274, 52, 10.1111/joim.12044 Kolehmainen, 2015, Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome, Am. J. Clin. Nutr., 101, 228, 10.3945/ajcn.114.092783 Baggio, 2007, Biology of incretins: GLP-1 and GIP, Gastroenterology, 132, 2131, 10.1053/j.gastro.2007.03.054 Gogebakan, 2015, GIP increases adipose tissue expression and blood levels of MCP-1 in humans and links high energy diets to inflammation: a randomised trial, Diabetologia, 58, 1759, 10.1007/s00125-015-3618-4 Milner, 2012, The impact of obesity on the immune response to infection, Proc. Nutr. Soc., 71, 298, 10.1017/S0029665112000158 Donath, 2011, Type 2 diabetes as an inflammatory disease, Nat. Rev. Immunol., 11, 98, 10.1038/nri2925 Phung, 2013, Body mass index and risk of pneumonia: a systematic review and meta-analysis, Obes. Rev., 14, 839, 10.1111/obr.12055