Toll-like receptors: linking inflammation to metabolism

WHO. (2006) Obesity and overweight. Fact sheet number 311. http://www.who.int/mediacentre/factsheets/fs311/en/index.html

Mokdad, 2003, Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001, JAMA, 289, 76, 10.1001/jama.289.1.76

Ferreira, 2010, High-carbohydrate diet selectively induces tumor necrosis factor-alpha production in mice liver, Inflammation

Hotamisligil, 2006, Inflammation and metabolic disorders, Nature, 444, 860, 10.1038/nature05485

Plum, 2005, The role of insulin receptor signaling in the brain, Trends Endocrinol. Metab., 16, 59, 10.1016/j.tem.2005.01.008

Plum, 2006, Central insulin action in energy and glucose homeostasis, J. Clin. Invest., 116, 1761, 10.1172/JCI29063

Galic, 2010, Adipose tissue as an endocrine organ, Mol. Cell Endocrinol., 316, 129, 10.1016/j.mce.2009.08.018

Wellen, 2005, Inflammation, stress, and diabetes, J. Clin. Invest., 115, 1111, 10.1172/JCI25102

Zhang, 1994, Positional cloning of the mouse obese gene and its human homologue, Nature, 372, 425, 10.1038/372425a0

Friedman, 2009, Leptin at 14 y of age: an ongoing story, Am. J. Clin. Nutr., 89, 973S, 10.3945/ajcn.2008.26788B

Friedman, 2009, Obesity: Causes and control of excess body fat, Nature, 459, 340, 10.1038/459340a

Gao, 2004, Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation, Proc. Natl. Acad. Sci. U. S. A., 101, 4661, 10.1073/pnas.0303992101

Belgardt, 2008, PDK1 deficiency in POMC-expressing cells reveals FOXO1-dependent and -independent pathways in control of energy homeostasis and stress response, Cell Metab., 7, 291, 10.1016/j.cmet.2008.01.006

Hill, 2008, Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice, J. Clin. Invest., 118, 1796, 10.1172/JCI32964

Bates, 2003, STAT3 signalling is required for leptin regulation of energy balance but not reproduction, Nature, 421, 856, 10.1038/nature01388

Niswender, 2001, Intracellular signalling. Key enzyme in leptin-induced anorexia, Nature, 413, 794, 10.1038/35101657

Bjorbaek, 1999, The role of SOCS-3 in leptin signaling and leptin resistance, J. Biol. Chem., 274, 30059, 10.1074/jbc.274.42.30059

Bence, 2006, Neuronal PTP1B regulates body weight, adiposity and leptin action, Nat. Med., 12, 917, 10.1038/nm1435

Ernst, 2009, Enhanced Stat3 activation in POMC neurons provokes negative feedback inhibition of leptin and insulin signaling in obesity, J. Neurosci., 2, 11582, 10.1523/JNEUROSCI.5712-08.2009

Rother, 2008, Neurocircuits integrating hormone and nutrient signaling in control of glucose metabolism, Am. J. Physiol. Endocrinol. Metab., 294, E810, 10.1152/ajpendo.00685.2007

Sanchez-Lasheras, 2010, Integrative neurobiology of energy homeostasis-neurocircuits, signals and mediators, Front Neuroendocrinol., 31, 4, 10.1016/j.yfrne.2009.08.002

Gropp, 2005, Agouti-related peptide-expressing neurons are mandatory for feeding, Nat. Neurosci., 8, 1289, 10.1038/nn1548

Luquet, 2005, NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates, Science, 310, 683, 10.1126/science.1115524

Gao, 2007, Neurobiology of feeding and energy expenditure, Annu. Rev. Neurosci., 30, 367, 10.1146/annurev.neuro.30.051606.094324

Plum, 2006, Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity, J. Clin. Invest., 116, 1886, 10.1172/JCI27123

Plum, 2007, Enhanced leptin-stimulated Pi3k activation in the CNS promotes white adipose tissue transdifferentiation, Cell Metab., 6, 431, 10.1016/j.cmet.2007.10.012

El-Haschimi, 2000, Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity, J. Clin. Invest., 105, 1827, 10.1172/JCI9842

Kahn, 1994, Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes, Diabetes, 43, 1066, 10.2337/diab.43.8.1066

White, 2003, Insulin signaling in health and disease, Science, 302, 1710, 10.1126/science.1092952

Schwartz, 2006, Central nervous system regulation of food intake, Obesity (Silver Spring), 14, 1, 10.1038/oby.2006.275

Bruning, 2000, Role of brain insulin receptor in control of body weight and reproduction, Science, 289, 2122, 10.1126/science.289.5487.2122

Koch, 2008, Central insulin action regulates peripheral glucose and fat metabolism in mice, J. Clin. Invest., 118, 2132

Konner, 2007, Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production, Cell Metab., 5, 438, 10.1016/j.cmet.2007.05.004

Obici, 2002, Hypothalamic insulin signaling is required for inhibition of glucose production, Nat. Med., 8, 1376, 10.1038/nm1202-798

Konner, 2009, Control of energy homeostasis by insulin and leptin: targeting the arcuate nucleus and beyond, Physiol. Behav., 97, 632, 10.1016/j.physbeh.2009.03.027

Niswender, 2003, Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities, Front Neuroendocrinol., 24, 1, 10.1016/S0091-3022(02)00105-X

Seino, 2003, Physiological and pathophysiological roles of ATP-sensitive K+ channels, Prog. Biophys. Mol. Biol., 81, 133, 10.1016/S0079-6107(02)00053-6

Uysal, 1997, Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function, Nature, 389, 610, 10.1038/39335

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

Matthews, 2010, Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance, Diabetologia, 10.1007/s00125-010-1865-y

Netea, 2006, Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance, Nat. Med., 12, 650, 10.1038/nm1415

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

Hirosumi, 2002, A central role for JNK in obesity and insulin resistance, Nature, 420, 333, 10.1038/nature01137

Arkan, 2005, IKK-beta links inflammation to obesity-induced insulin resistance, Nat. Med., 11, 191, 10.1038/nm1185

Schmitz-Peiffer, 2008, Protein kinase C function in muscle, liver, and beta-cells and its therapeutic implications for type 2 diabetes, Diabetes, 57, 1774, 10.2337/db07-1769

Ozcan, 2004, Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes, Science, 306, 457, 10.1126/science.1103160

Prada, 2005, Western diet modulates insulin signaling, c-Jun N-terminal kinase activity, and insulin receptor substrate-1ser307 phosphorylation in a tissue-specific fashion, Endocrinology, 146, 1576, 10.1210/en.2004-0767

Belgardt, 2010, Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism, Proc. Natl. Acad. Sci. U. S. A., 107, 6028, 10.1073/pnas.1001796107

Aguirre, 2000, The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307), J. Biol. Chem., 275, 9047, 10.1074/jbc.275.12.9047

Shoelson, 2003, Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance, Int. J. Obes. Relat. Metab. Disord., 27, S49, 10.1038/sj.ijo.0802501

Gao, 2002, Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex, J. Biol. Chem., 277, 48115, 10.1074/jbc.M209459200

Cai, 2005, Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB, Nat. Med., 11, 183, 10.1038/nm1166

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

Wunderlich, 2008, Hepatic NF-kappa B essential modulator deficiency prevents obesity-induced insulin resistance but synergizes with high-fat feeding in tumorigenesis, Proc. Natl. Acad. Sci. U. S. A., 105, 1297, 10.1073/pnas.0707849104

Chibalin, 2008, Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance, Cell, 132, 375, 10.1016/j.cell.2007.12.035

Houstis, 2006, Reactive oxygen species have a causal role in multiple forms of insulin resistance, Nature, 440, 944, 10.1038/nature04634

Lin, 2005, The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species, J. Biol. Chem., 280, 4617, 10.1074/jbc.M411863200

Stein, 2004, The epidemic of obesity, J. Clin. Endocrinol. Metab., 89, 2522, 10.1210/jc.2004-0288

Shi, 2006, TLR4 links innate immunity and fatty acid-induced insulin resistance, J. Clin. Invest., 116, 3015, 10.1172/JCI28898

Poggi, 2007, C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet, Diabetologia, 50, 1267, 10.1007/s00125-007-0654-8

Tsukumo, 2007, Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance, Diabetes, 56, 1986, 10.2337/db06-1595

Kim, 2007, Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity, Circ. Res., 100, 1589, 10.1161/CIRCRESAHA.106.142851

Staiger, 2004, Palmitate-induced interleukin-6 expression in human coronary artery endothelial cells, Diabetes, 53, 3209, 10.2337/diabetes.53.12.3209

Senn, 2006, Toll-like receptor-2 is essential for the development of palmitate-induced insulin resistance in myotubes, J. Biol. Chem., 281, 26865, 10.1074/jbc.M513304200

Nguyen, 2007, A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways, J. Biol. Chem., 282, 35279, 10.1074/jbc.M706762200

Schaeffler, 2009, Fatty. acid-induced induction of Toll-like receptor-4/nuclear factor-kappaB pathway in adipocytes links nutritional signalling with innate immunity, Immunology, 126, 233, 10.1111/j.1365-2567.2008.02892.x

Kumar, 2009, Toll-like receptors and innate immunity, Biochem. Biophys. Res. Commun., 388, 621, 10.1016/j.bbrc.2009.08.062

Medzhitov, 2001, Toll-like receptors and innate immunity, Nat. Rev. Immunol., 1, 135, 10.1038/35100529

Kawai, 1999, Unresponsiveness of MyD88-deficient mice to endotoxin, Immunity, 11, 115, 10.1016/S1074-7613(00)80086-2

Kawai, 2006, TLR signaling, Cell Death Differ., 13, 816, 10.1038/sj.cdd.4401850

Yamamoto, 2003, Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway, Science, 301, 640, 10.1126/science.1087262

Pasare, 2004, Toll-like receptors: linking innate and adaptive immunity, Microbes Infect., 6, 1382, 10.1016/j.micinf.2004.08.018

Lee, 2001, Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4, J. Biol. Chem., 276, 16683, 10.1074/jbc.M011695200

Lee, 2003, Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids, J. Biol. Chem., 278, 37041, 10.1074/jbc.M305213200

Hwang, 2001, Modulation of the expression of cyclooxygenase-2 by fatty acids mediated through toll-like receptor 4-derived signaling pathways, Faseb. J., 15, 2556, 10.1096/fj.01-0432com

Hommelberg, 2009, Fatty. acid-induced NF-{kappa}B activation and insulin resistance in skeletal muscle are chain length dependent, Am. J. Physiol. Endocrinol. Metab., 296, E114, 10.1152/ajpendo.00436.2007

Lockridge, 2008, Bioinformatic profiling of the transcriptional response of adult rat cardiomyocytes to distinct fatty acids, J. Lipid. Res., 49, 1395, 10.1194/jlr.M700517-JLR200

Davis, 2008, Tlr-4 deficiency selectively protects against obesity induced by diets high in saturated fat, Obesity (Silver Spring), 16, 1248, 10.1038/oby.2008.210

Takeuchi, 2010, Pattern recognition receptors and inflammation, Cell, 140, 805, 10.1016/j.cell.2010.01.022

Caricilli, 2008, Inhibition of toll-like receptor 2 expression improves insulin sensitivity and signaling in muscle and white adipose tissue of mice fed a high-fat diet, J. Endocrinol., 199, 399, 10.1677/JOE-08-0354

Saberi, 2009, Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice, Cell Metab., 10, 419, 10.1016/j.cmet.2009.09.006

Reyna, 2008, Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects, Diabetes, 57, 2595, 10.2337/db08-0038

Erridge, 2009, Saturated fatty acids do not directly stimulate Toll-like receptor signaling, Arterioscler. Thromb. Vasc. Biol., 29, 1944, 10.1161/ATVBAHA.109.194050

Summers, 2005, A role for sphingolipids in producing the common features of type 2 diabetes, metabolic syndrome X, and Cushing's syndrome, Diabetes, 54, 591, 10.2337/diabetes.54.3.591

Holland, 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

Fischer, 2007, Ceramide as a TLR4 agonist; a putative signalling intermediate between sphingolipid receptors for microbial ligands and TLR4, Cell Microbiol., 9, 1239, 10.1111/j.1462-5822.2006.00867.x

Schwartz, 2010, Nutrient modification of the innate immune response: a novel mechanism by which saturated fatty acids greatly amplify monocyte inflammation, Arterioscler. Thromb. Vasc. Biol., 30, 802, 10.1161/ATVBAHA.109.201681

Cani, 2009, Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota, Curr. Opin. Pharmacol., 9, 737, 10.1016/j.coph.2009.06.016

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

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

Muoio, 2008, Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes, Nat. Rev. Mol. Cell Biol., 9, 193, 10.1038/nrm2327

De Souza, 2005, Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus, Endocrinology, 146, 4192, 10.1210/en.2004-1520

Schwartz, 2005, Diabetes, obesity, and the brain, Science, 307, 375, 10.1126/science.1104344

Sandoval, 2008, The integrative role of CNS fuel-sensing mechanisms in energy balance and glucose regulation, Annu. Rev. Physiol., 70, 513, 10.1146/annurev.physiol.70.120806.095256

Woods, 2004, Consumption of a high-fat diet alters the homeostatic regulation of energy balance, Physiol. Behav., 83, 573, 10.1016/j.physbeh.2004.07.026

Enriori, 2007, Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons, Cell Metab., 5, 181, 10.1016/j.cmet.2007.02.004

Posey, 2008, Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet, Am. J. Physiol. Endocrinol. Metab., 296, E1003, 10.1152/ajpendo.90377.2008

Kleinridders, 2009, MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity, Cell Metab., 10, 249, 10.1016/j.cmet.2009.08.013

Zhang, 2008, Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity, Cell, 135, 61, 10.1016/j.cell.2008.07.043

Ozcan, 2009, Endoplasmic reticulum stress plays a central role in development of leptin resistance, Cell Metab., 9, 35, 10.1016/j.cmet.2008.12.004

Posey, 2009, Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet, Am. J. Physiol. Endocrinol. Metab., 296, E1003, 10.1152/ajpendo.90377.2008

Milanski, 2009, Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity, J. Neurosci., 29, 359, 10.1523/JNEUROSCI.2760-08.2009