Minireview: Inflammation and Obesity Pathogenesis: The Hypothalamus Heats Up

Obesity is associated with macrophage accumulation in adipose tissue

Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041

Inflammation and metabolic disorders

Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199

Prevalence and Trends in Obesity Among US Adults, 1999-2008

Flegal, K. M. (2010) · JAMA · doi:10.1001/jama.2009.2014 · Cited by 7,580

Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance

Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760

Metabolic Endotoxemia Initiates Obesity and Insulin Resistance

Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., Neyrinck, A. M., Fava, F., Tuohy, K. M., Chabo, C., et al. (2007) · Diabetes · doi:10.2337/db06-1491 · Cited by 6,638

Central nervous system control of food intake

Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451

Inflammation and insulin resistance

Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769

Effects of Bariatric Surgery on Mortality in Swedish Obese Subjects

Sjöström, L., Narbro, K., Sjöström, C. D., Karason, K., Larsson, B., Wedel, H., Lystig, T., Sullivan, M., Bouchard, C., Carlsson, B., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa066254 · Cited by 4,668

Annual Medical Spending Attributable To Obesity: Payer-And Service-Specific Estimates

Finkelstein, E. A., Trogdon, J. G., Cohen, J. W., & Dietz, W. H. (2009) · Health Affairs · doi:10.1377/hlthaff.28.5.w822 · Cited by 2,956

Long-term mortality after gastric bypass surgery

Adams, T. D., Gress, R. E., Smith, S. C., Halverson, R. C., Simper, S. C., Rosamond, W. D., LaMonte, M. J., Stroup, A. M., & Hunt, S. C. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa066603 · Cited by 2,572

Central nervous system control of food intake and body weight

Morton, G. J., Cummings, D. E., Baskin, D. G., Barsh, G. S., & Schwartz, M. W. (2006) · Nature · doi:10.1038/nature05026 · Cited by 2,503

Interleukin-1-receptor antagonist in type 2 diabetes mellitus

Larsen, C. M., Faulenbach, M., Vaag, A., Vølund, A., Ehses, J. A., Seifert, B., Mandrup-Poulsen, T., & Donath, M. Y. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa065213 · Cited by 1,798

Hypothalamic IKKβ/NF-κB and ER Stress Link Overnutrition to Energy Imbalance and Obesity

Zhang, X., Zhang, G., Zhang, H., Karin, M., Bai, H., & Cai, D. (2008) · Cell · doi:10.1016/j.cell.2008.07.043 · Cited by 1,350

Insulin sensitivity: Modulation by nutrients and inflammation

Schenk, S., Saberi, M., & Olefsky, J. M. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34260 · Cited by 1,191

Consumption of a Fat-Rich Diet Activates a Proinflammatory Response and Induces Insulin Resistance in the Hypothalamus

De Souza, C. T., Araujo, E. P., Bordin, S., Ashimine, R., Zollner, R. L., Boschero, A. C., Saad, M. J. A., & Velloso, L. A. (2005) · Endocrinology · doi:10.1210/en.2004-1520 · Cited by 1,171

Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity

Milanski, M., Degasperi, G., Coope, A., Morari, J., Denis, R., Cintra, D. E., Tsukumo, D. M. L., Anhe, G., Amaral, M. E., Takahashi, H. K., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2760-08.2009 · Cited by 1,125

Mechanisms of leptin action and leptin resistance.

Myers, M. G., Cowley, M. A., & Münzberg, H. (2008) · Annual Review of Physiology · doi:10.1146/annurev.physiol.70.113006.100707 · Cited by 1,074

Nutrient sensing and inflammation in metabolic diseases

Hotamisligil, G. S., & Erbay, E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2449 · Cited by 1,040

Increased Inflammatory Properties of Adipose Tissue Macrophages Recruited During Diet-Induced Obesity

Lumeng, C. N., DeYoung, S. M., Bodzin, J. L., & Saltiel, A. R. (2007) · Diabetes · doi:10.2337/db06-1076 · Cited by 1,016

Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance

Ozcan, L., Ergin, A. S., Lu, A., Chung, J., Sarkar, S., Nie, D., Myers, M. G., & Ozcan, U. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.004 · Cited by 875

Comparison of Strategies for Sustaining Weight Loss<subtitle>The Weight Loss Maintenance Randomized Controlled Trial</subtitle>

Svetkey, L. P. (2008) · JAMA · doi:10.1001/jama.299.10.1139 · Cited by 748

Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice

Münzberg, H., Flier, J. S., & Bjørbæk, C. (2004) · Endocrinology · doi:10.1210/en.2004-0726 · Cited by 737

Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity

Mori, H., Hanada, R., Hanada, T., Aki, D., Mashima, R., Nishinakamura, H., Torisu, T., Chien, K. R., Yasukawa, H., & Yoshimura, A. (2004) · Nature Medicine · doi:10.1038/nm1071 · Cited by 651

Neuronal PTP1B regulates body weight, adiposity and leptin action

Bence, K. K., Delibegovic, M., Xue, B., Gorgun, C. Z., Hotamisligil, G. S., Neel, B. G., & Kahn, B. B. (2006) · Nature Medicine · doi:10.1038/nm1435 · Cited by 633

Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet

Posey, K. A., Clegg, D. J., Printz, R. L., Byun, J., Morton, G. J., Vivekanandan-Giri, A., Pennathur, S., Baskin, D. G., Heinecke, J. W., Woods, S. C., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90377.2008 · Cited by 586

Toll-Like Receptor-4 Mediates Vascular Inflammation and Insulin Resistance in Diet-Induced Obesity

Kim, F., Pham, M., Luttrell, I., Bannerman, D. D., Tupper, J., Thaler, J., Hawn, T. R., Raines, E. W., & Schwartz, M. W. (2007) · Circulation Research · doi:10.1161/circresaha.106.142851 · Cited by 584

Genetics of Obesity in Humans

Farooqi, I. S., & O’Rahilly, S. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0040 · Cited by 583

Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3

Howard, J. K., Cave, B. J., Oksanen, L. J., Tzameli, I., Bjørbæk, C., & Flier, J. S. (2004) · Nature Medicine · doi:10.1038/nm1072 · Cited by 490

MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity

Kleinridders, A., Schenten, D., Könner, A. C., Belgardt, B. F., Mauer, J., Okamura, T., Wunderlich, F. T., Medzhitov, R., & Brüning, J. C. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.013 · Cited by 483

Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity

Unger, R. H., & Scherer, P. E. (2010) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2010.01.009 · Cited by 436

High-Fat Diet Induces Apoptosis of Hypothalamic Neurons

Moraes, J. C., Coope, A., Morari, J., Cintra, D. E., Roman, E. A., Pauli, J. R., Romanatto, T., Carvalheira, J. B. C., de Oliveira, A. L. R., Saad, M. J. A., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005045 · Cited by 427

Low Dose Leptin Administration Reverses Effects of Sustained Weight-Reduction on Energy Expenditure and Circulating Concentrations of Thyroid Hormones

Rosenbaum, M., Murphy, E. M., Heymsfield, S. B., Matthews, D. E., & Leibel, R. L. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.5.2391 · Cited by 407

Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo.

Zabolotny, J. M., Kim, Y.-B., Welsh, L. A., Kershaw, E. E., Neel, B. G., & Kahn, B. B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800061200 · Cited by 404

Attenuation of leptin and insulin signaling by SOCS proteins

Howard, J. K., & Flier, J. S. (2006) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2006.09.007 · Cited by 382

Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

Benoit, S. C., Kemp, C. J., Elias, C. F., Abplanalp, W., Herman, J. P., Migrenne, S., Lefevre, A.-L., Cruciani-Guglielmacci, C., Magnan, C., Yu, F., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36714 · Cited by 351

Tlr-4 deficiency selectively protects against obesity induced by diets high in saturated fat

Davis, J. E., Gabler, N. K., Walker‐Daniels, J., & Spurlock, M. E. (2008) · Obesity · doi:10.1038/oby.2008.210 · Cited by 334

Use of Salsalate to Target Inflammation in the Treatment of Insulin Resistance and Type 2 Diabetes

Goldfine, A. B., Silver, R., Aldhahi, W., Cai, D., Tatro, E., Lee, J., & Shoelson, S. E. (2008) · Clinical and Translational Science · doi:10.1111/j.1752-8062.2008.00026.x · Cited by 293

High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex

ZHANG, X., Dong, F., Ren, J. T., Driscoll, M., & Culver, B. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.10.011 · Cited by 290

Update on Obesity

Bessesen, D. H. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0520 · Cited by 257

Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome

Fessler, M. B., Rudel, L. L., & Brown, J. M. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32832fa5c4 · Cited by 256

Defense of differfing body weight set points in diet-induced obese and resistant rats

Levin, B. E., & Keesey, R. E. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.2.r412 · Cited by 245

PTP1B and SHP2 in POMC neurons reciprocally regulate energy balance in mice

Banno, R., Zimmer, D., De Jonghe, B. C., Atienza, M., Rak, K., Yang, W., & Bence, K. K. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39620 · Cited by 214

Enhanced Stat3 Activation in POMC Neurons Provokes Negative Feedback Inhibition of Leptin and InsulinSignaling in Obesity

Ernst, M. B., Wunderlich, C. M., Hess, S., Paehler, M., Mesaros, A., Koralov, S. B., Kleinridders, A., Husch, A., Münzberg, H., Hampel, B., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5712-08.2009 · Cited by 185

Functional Role of Suppressor of Cytokine Signaling 3 Upregulation in Hypothalamic Leptin Resistance and Long-Term Energy Homeostasis

Reed, A. S., Unger, E. K., Olofsson, L. E., Piper, M. L., Myers, M. G., & Xu, A. W. (2010) · Diabetes · doi:10.2337/db09-1024 · Cited by 176

Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism

Belgardt, B., Mauer, J., Wunderlich, F. T., Ernst, M. B., Pál, M., Spohn, G., Brönneke, H. S., Brodesser, S., Hampel, B., Schauss, A. C., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001796107 · Cited by 171

Human IL6 enhances leptin action in mice

Sadagurski, M., Norquay, L., Farhang, J., D’Aquino, K. E., Copps, K. D., & White, M. F. (2009) · Diabetologia · doi:10.1007/s00125-009-1580-8 · Cited by 160

HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms

White, C. L., Whittington, A., Barnes, M. J., Wang, Z., Bray, G. A., & Morrison, C. D. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90513.2008 · Cited by 150

Hypothalamic inflammation and energy homeostasis: Resolving the paradox

Thaler, J. P., Choi, S. J., Schwartz, M. W., & Wisse, B. E. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.002 · Cited by 144

An Integrative View of Obesity

Wisse, B. E., Kim, F., & Schwartz, M. W. (2007) · Science · doi:10.1126/science.1148032 · Cited by 138

Reduction of Hypothalamic Protein Tyrosine Phosphatase Improves Insulin and Leptin Resistance in Diet-Induced Obese Rats

Picardi, P. K., Calegari, V. C., Prada, P. O., Moraes, J. C., ARAUJO, E. P. D., Gomes‐Marcondes, M. C. C., Ueno, M., Carvalheira, J. B. C., Velloso, L. A., & Saad, M. J. A. (2008) · Endocrinology · doi:10.1210/en.2007-1506 · Cited by 133

TNF-α acts in the hypothalamus inhibiting food intake and increasing the respiratory quotient—Effects on leptin and insulin signaling pathways

Romanatto, T., Cesquini, M., do Amaral, M. E. C., Roman, É. A., Moraes, J. C., Torsoni, M. A., Cruz-Neto, A. P., & Velloso, L. A. (2007) · Peptides · doi:10.1016/j.peptides.2007.03.006 · Cited by 131

Molecular physiology of weight regulation in mice and humans

Leibel, R. L. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.245 · Cited by 120

Role of the hypothalamic–pituitary–thyroid axis in metabolic regulation by JNK1Preprint

Sabio, G., Cavanagh, J., Barrett, T., Jung, D. Y., Ko, H. J., Ong, H., Morel, C., Mora, A., Reilly, J., Kim, J. K., et al. (2010) · Genes & Development · doi:10.1101/gad.1878510 · Cited by 119

Changes in Hypothalamically Mediated Acute-Phase Inflammatory Responses to Lipopolysaccharide in Diet-Induced Obese Rats

Pohl, J., Woodside, B. C., & Luheshi, G. N. (2009) · Endocrinology · doi:10.1210/en.2009-0526 · Cited by 74

Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids

Choi, S. J., Kim, F., Schwartz, M. W., & Wisse, B. E. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00006.2010 · Cited by 73

Modulation of central leptin sensitivity and energy balance in a rat model of diet‐induced obesity

Fam, B. C., Morris, M. J., Hansen, M. J., Kebede, M. A., Andrikopoulos, S., Proietto, J., & Thorburn, A. W. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00653.x · Cited by 72

Atypical Protein Kinase C Activity in the Hypothalamus Is Required for Lipopolysaccharide-Mediated Sickness Responses

Thaler, J. P., Choi, S. J., Sajan, M. P., Ogimoto, K., Hồng, N. T., Matsen, M. E., Benoit, S. C., Wisse, B. E., Farese, R. V., & Schwartz, M. W. (2009) · Endocrinology · doi:10.1210/en.2009-0509 · Cited by 27

The effect of anti‐inflammatory (aspirin and/or statin) therapy on body weight in Type 2 diabetic individuals: EAT, a retrospective study

Boaz, M., Lisy, L., Zandman‐Goddard, G., & Wainstein, J. (2009) · Diabetic Medicine · doi:10.1111/j.1464-5491.2009.02747.x · Cited by 22

Inflammatory links between obesity and metabolic disease

Lumeng, C. N., & Saltiel, A. R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57132 · Cited by 2,319

Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future

Kahn, S. E., Cooper, M. E., & Del Prato, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62154-6 · Cited by 1,743

Obesity is associated with hypothalamic injury in rodents and humans.

Thaler, J. P., Yi, C.-X., Schur, E. A., Guyenet, S. J., Hwang, B. H., Dietrich, M. O., Zhao, X., Sarruf, D. A., Izgur, V., Maravilla, K. R., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59660 · Cited by 1,857

Immune system to brain signaling: Neuropsychopharmacological implications

Capuron, L., & Miller, A. H. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.01.014 · Cited by 1,195

Obesity and neuroinflammation: A pathway to cognitive impairment

Miller, A. A., & Spencer, S. J. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.04.001 · Cited by 834

Inflammation and Obesity Pathogenesis: The Hypothalamus Heats Up

Thaler, J. P., & Schwartz, M. W. (2010) · Endocrine Reviews · doi:10.1210/edrv.31.4.9998 · Cited by 19

Does Hypothalamic Inflammation Cause Obesity?

Wisse, B. E., & Schwartz, M. W. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.003 · Cited by 62

Diet-Induced Inflammation of the Hypothalamus in Obesity

Velloso, L. A., ARAUJO, E. P. D., & de Souza, C. T. (2008) · NeuroImmunoModulation · doi:10.1159/000153423 · Cited by 135

Hypothalamic inflammation in obesity and metabolic disease

Jais, A., & Brüning, J. C. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88878 · Cited by 474

Central administration of interleukin-4 exacerbates hypothalamic inflammation and weight gain during high-fat feeding

Oh‐I, S., Thaler, J. P., Ogimoto, K., Wisse, B. E., Morton, G. J., & Schwartz, M. W. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00026.2010 · Cited by 68