Diabetes, Obesity, and the Brain

Positional cloning of the mouse obese gene and its human homologue

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Central nervous system control of food intake

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Congenital leptin deficiency is associated with severe early-onset obesity in humans

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Cellular mechanisms of insulin resistance

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Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus

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Role of Brain Insulin Receptor in Control of Body Weight and Reproduction

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Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein

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AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus

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Leptin-Replacement Therapy for Lipodystrophy

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Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons

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Reduced Food Intake and Body Weight in Mice Treated with Fatty Acid Synthase Inhibitors

Loftus, T. M., Jaworsky, D. E., Frehywot, G. L., Townsend, C. A., Ronnett, G. V., Lane, M. D., & Kuhajda, F. P. (2000) · Science · doi:10.1126/science.288.5475.2379 · Cited by 1,004 · see citing works

Minireview: The AMP-Activated Protein Kinase Cascade: The Key Sensor of Cellular Energy Status

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Specificity of Leptin Action on Elevated Blood Glucose Levels and Hypothalamic Neuropeptide Y Gene Expression in <i>ob/ob</i> Mice

Schwartz, M. W., Baskin, D. G., Bukowski, T. R., Kuijper, J. L., Foster, D., Lasser, G., Prunkard, D. E., Porte, D., Woods, S. C., Seeley, R. J., et al. (1996) · Diabetes · doi:10.2337/diab.45.4.531 · Cited by 904 · see citing works

Hypothalamic insulin signaling is required for inhibition of glucose production

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Leptin Increases Hypothalamic Pro-opiomelanocortin mRNA Expression in the Rostral Arcuate Nucleus

Schwartz, M. W., Seeley, R. J., Woods, S. C., Weigle, D. S., Campfield, L. A., Burn, P., & Baskin, D. G. (1997) · Diabetes · doi:10.2337/diab.46.12.2119 · Cited by 879 · see citing works

Insulin in the Brain: A Hormonal Regulator of Energy Balance*

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Identification of the gene altered in Berardinelli–Seip congenital lipodystrophy on chromosome 11q13

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Insulin signaling in health and disease

White, M. F. (2003) · Science · doi:10.1126/science.1092952 · Cited by 733 · see citing works

Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats

Obici, S., Feng, Z., Karkanias, G., Baskin, D. G., & Rossetti, L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-861 · Cited by 719 · see citing works

Suppressor of Cytokine Signaling 1 (SOCS-1) and SOCS-3 Cause Insulin Resistance through Inhibition of Tyrosine Phosphorylation of Insulin Receptor Substrate Proteins by Discrete Mechanisms

Ueki, K., Kondo, T., & Kahn, C. R. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.12.5434-5446.2004 · Cited by 686 · see citing works

Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice.Preprint

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Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake

Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., & Rossetti, L. (2002) · Diabetes · doi:10.2337/diabetes.51.2.271 · Cited by 654 · see citing works

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 · see citing works

Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats

Obici, S., Feng, Z., Karkanias, G. B., et al. (2002) · Nature Neuroscience · doi:10.1038/nn861 · Cited by 572 · see citing works

Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production

Obici, S., Feng, Z., Arduini, A., Conti, R., & Rossetti, L. (2003) · Nature Medicine · doi:10.1038/nm873 · Cited by 548 · see citing works

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 · see citing works

Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus

Niswender, K. D., Morrison, C. D., Clegg, D. J., Olson, R., Baskin, D. G., Myers, M. G., Seeley, R. J., & Schwartz, M. W. (2003) · Diabetes · doi:10.2337/diabetes.52.2.227 · Cited by 476 · see citing works

Neuropeptide Y Stimulates Feeding but Inhibits Sexual Behavior in Rats*

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The Central Melanocortin System and Energy Homeostasis

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Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes

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A Leptin Dose-Response Study in Obese (ob/ob) and Lean (+/?) Mice

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C75, a Fatty Acid Synthase Inhibitor, Reduces Food Intake via Hypothalamic AMP-activated Protein Kinase*

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Hypothalamic malonyl-CoA as a mediator of feeding behavior

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Arctic waders are not capital breeders

Klaassen, M., Lindström, Å., Meltofte, H., & Piersma, T. (2001) · Nature · doi:10.1038/35101654 · Cited by 261 · see citing works

Fatty acid metabolism and insulin secretion in pancreatic beta cells

Yaney, G. C., & Corkey, B. E. (2003) · Diabetologia · doi:10.1007/s00125-003-1207-4 · Cited by 251 · see citing works

Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy

Maldergem, L. V., Magré, J., Khallouf, T. E., Gedde‐Dahl, T., Délepine, M., Trygstad, O., Seemanová, E., Stephenson, T. J., Albott, C. S., Bonńici, F., et al. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.10.722 · Cited by 250 · see citing works

Transgenic Overexpression of Leptin Rescues Insulin Resistance and Diabetes in a Mouse Model of Lipoatrophic Diabetes

Ebihara, K., Ogawa, Y., Masuzaki, H., Shintani, M., Miyanaga, F., Aizawa‐Abe, M., Hayashi, T., Hosoda, K., Inoue, G., Yoshimasa, Y., et al. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1440 · Cited by 240 · see citing works

Insulin receptor substrate 2 plays a crucial role in β cells and the hypothalamus

Kubota, N., Terauchi, Y., Tobe, K., Yano, W., Suzuki, R., Ueki, K., Takamoto, I., Satoh, H., Maki, T., Kubota, T., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21484 · Cited by 239 · see citing works

Monitoring of stored and available fuel by the CNS: implications for obesity

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Site and mechanism of leptin action in a rodent form of congenital lipodystrophy

Asilmaz, E., Cohen, P., Miyazaki, M., Dobrzyn, P., Ueki, K., Fayzikhodjaeva, G., Soukas, A. A., Kahn, C. R., Ntambi, J. M., Socci, N. D., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419511 · Cited by 210 · see citing works

Lipoatrophy Revisited

Reitman, M. L., Arioglu, E., Gavrilova, O., & Taylor, S. I. (2000) · Trends in Endocrinology &amp; Metabolism · doi:10.1016/s1043-2760(00)00309-x · Cited by 193 · see citing works

The Effect of Insulin on In Vivo Cerebral Glucose Concentrations and Rates of Glucose Transport/Metabolism in Humans

Seaquist, E. R., Damberg, G., Tkáč, I., & Rolf Gruetter, A. (2001) · Diabetes · doi:10.2337/diabetes.50.10.2203 · Cited by 185 · see citing works

Transgenic rescue of insulin receptor–deficient mice

Okamoto, H., Nakae, J., Kitamura, T., Park, B.-C., Dragatsis, I., & Accili, D. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200421645 · Cited by 151 · see citing works

Metabolic control of -cell function

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Intracerebroventricular Neuropeptide Y Infusion Precludes Inhibition of Glucose and VLDL Production by Insulin

van den Hoek, A. M., Voshol, P. J., Karnekamp, B. N., Buijs, R. M., Romijn, J. A., Havekes, L. M., & Pijl, H. (2004) · Diabetes · doi:10.2337/diabetes.53.10.2529 · Cited by 109 · see citing works

Hypothalamic, Metabolic, and Behavioral Responses to Pharmacological Inhibition of CNS Melanocortin Signaling in Rats

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Adiposity Signaling and Biological Defense Against Weight Gain: Absence of Protection or Central Hormone Resistance?

Schwartz, M. W., & Niswender, K. D. (2004) · The Journal of Clinical Endocrinology &amp; Metabolism · doi:10.1210/jc.2004-0906 · Cited by 93 · see citing works

Suppressor of Cytokine Signaling 1 (SOCS-1) and SOCS-3 Cause Insulin Resistance through Inhibition of Tyrosine Phosphorylation of Insulin Receptor Substrate Proteins by Discrete Mechanisms

Ueki, K., Kondo, T., & Kahn, C. R. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.19.8762.2005 · Cited by 85 · see citing works

The role of leptin-->STAT3 signaling in neuroendocrine function: an integrative perspective

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Intracerebroventricular Neuropeptide Y Acutely Influences Glucose Metabolism and Insulin Sensitivity in the Rat

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The Anorexigenic Fatty Acid Synthase Inhibitor, C75, Is a Nonspecific Neuronal Activator

Takahashi, K. A., Smart, J. L., Liu, H., & Cone, R. D. (2003) · Endocrinology · doi:10.1210/en.2003-0337 · Cited by 42 · see citing works

From lipodystrophy syndromes to diabetes mellitus

Joffe, B. I., Panz, V. R., & Raal, F. J. (2001) · The Lancet · doi:10.1016/s0140-6736(00)04616-x · Cited by 40 · see citing works

Current Awareness

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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 · see citing works

Insulin sensitivity: Modulation by nutrients and inflammation

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Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake

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Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis

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Insulin Action in AgRP-Expressing Neurons Is Required for Suppression of Hepatic Glucose Production

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Gonadal Hormones Determine Sensitivity to Central Leptin and Insulin

Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1339 · Cited by 552 · see citing works

Regulation of lipid stores and metabolism by lipophagy

Liu, K., & Czaja, M. J. (2013) · Cell Death &amp; Differentiation · doi:10.1038/cdd.2012.63 · Cited by 542 · see citing works

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 · see citing works

Central nervous system control of metabolism

Myers, M. G., & Olson, D. P. (2012) · Nature · doi:10.1038/nature11705 · Cited by 399 · see citing works

Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity

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Drug Insight: the role of leptin in human physiology and pathophysiology—emerging clinical applications

Brennan, A. M., & Mantzoros, C. S. (2006) · Nature Clinical Practice Endocrinology &amp; Metabolism · doi:10.1038/ncpendmet0196 · Cited by 374 · see citing works

Segregation of Acute Leptin and Insulin Effects in Distinct Populations of Arcuate Proopiomelanocortin Neurons

Williams, K. W., Margatho, L. O., Lee, C. E., Choi, M., Lee, S., Scott, M. M., Elias, C. F., & Elmquist, J. K. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3118-09.2010 · Cited by 352 · see citing works

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 · see citing works

How cognition modulates affective responses to taste and flavor: top-down influences on the orbitofrontal and pregenual cingulate cortices

Grabenhorst, F., Rolls, E. T., & Bilderbeck, A. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhm185 · Cited by 337 · see citing works

Regulation of Blood Glucose by Hypothalamic Pyruvate Metabolism

Lam, T. K. T., Gutierrez-Juarez, R., Pocai, A., & Rossetti, L. (2005) · Science · doi:10.1126/science.1112085 · Cited by 341 · see citing works

Leptin and the Central Nervous System Control of Glucose Metabolism

Morton, G. J., & Schwartz, M. W. (2011) · Physiological Reviews · doi:10.1152/physrev.00007.2010 · Cited by 338 · see citing works

Central effects of estradiol in the regulation of food intake, body weight, and adiposity

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Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link

Zhang, Y., Huang, N.-Q., Yan, F., Jin, H., Zhou, S.-Y., Shi, J.-S., & Jin, F. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.11.015 · Cited by 301 · see citing works

Carbohydrate intake and obesity

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The adipocyte as an active participant in energy balance and metabolism

Badman, M. K., & Flier, J. S. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.058 · Cited by 256 · see citing works

Does inadequate sleep play a role in vulnerability to obesity?

Knutson, K. L. (2012) · American Journal of Human Biology · doi:10.1002/ajhb.22219 · Cited by 241 · see citing works

A glucagon-like endocrine pathway in<i>Drosophila</i>modulates both lipid and carbohydrate homeostasis

Bharucha, K. N., Tarr, P., & Zipursky, S. L. (2008) · Journal of Experimental Biology · doi:10.1242/jeb.016451 · Cited by 239 · see citing works

Molecular disruption of hypothalamic nutrient sensing induces obesity

He, W., Lam, T. K. T., Obici, S., & Rossetti, L. (2006) · Nature Neuroscience · doi:10.1038/nn1626 · Cited by 233 · see citing works

Gender-specific care of the patient with diabetes: review and recommendations

Legato, M. J., Gelzer, A., Goland, R., Ebner, S. A., Rajan, S., Villagra, V., & Kosowski, M. (2006) · Gender Medicine · doi:10.1016/s1550-8579(06)80202-0 · Cited by 225 · see citing works

Uncoupling the mechanisms of obesity and hypertension by targeting hypothalamic IKK-β and NF-κB

Purkayastha, S., Zhang, G., & Cai, D. (2011) · Nature Medicine · doi:10.1038/nm.2372 · Cited by 220 · see citing works

Functions of the orbitofrontal and pregenual cingulate cortex in taste, olfaction, appetite and emotion

Rolls, E. (2008) · Acta Physiologica Hungarica · doi:10.1556/aphysiol.95.2008.2.1 · Cited by 214 · see citing works

Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats

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Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance

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Cardiac contractile dysfunction in Lep/Lep obesity is accompanied by NADPH oxidase activation, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain isozyme switch

Li, S.-Y., Yang, X., Ceylan-Isik, A. F., Du, M., Sreejayan, N., & Ren, J. (2006) · Diabetologia · doi:10.1007/s00125-006-0229-0 · Cited by 187 · see citing works

The Integrative Role of CNS Fuel-Sensing Mechanisms in Energy Balance and Glucose Regulation

Sandoval, D., Cota, D., & Seeley, R. J. (2008) · Annual Review of Physiology · doi:10.1146/annurev.physiol.70.120806.095256 · Cited by 178 · see citing works

Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood

Lee, S.-H., Zabolotny, J. M., Huang, H., Lee, H., & Kim, Y.-B. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.011 · Cited by 176 · see citing works

Circadian intervention of obesity development via resting-stage feeding manipulation or oxytocin treatment

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Brain regulation of energy balance and body weight

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Food intake and reward mechanisms in patients with schizophrenia: implications for metabolic disturbances and treatment with second-generation antipsychotic agents

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Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes

Gelling, R. W., Morton, G. J., Morrison, C. D., Niswender, K. D., Myers, M. G., Rhodes, C. J., & Schwartz, M. W. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2005.11.013 · Cited by 169 · see citing works

A causal role for hyperinsulinemia in obesity

Templeman, N. M., Skovsø, S., Page, M. M., Lim, G. E., & Johnson, J. D. (2017) · Journal of Endocrinology · doi:10.1530/joe-16-0449 · Cited by 168 · see citing works

Sympathetic nervous system behavior in human obesity

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Obese men respond to cognitive but not to catabolic brain insulin signaling

Hallschmid, M., Benedict, C., Schultes, B., Born, J., & Kern, W. (2008) · International Journal of Obesity · doi:10.1038/sj.ijo.0803722 · Cited by 165 · see citing works

Hypothalamic Leptin Signaling Regulates Hepatic Insulin Sensitivity via a Neurocircuit Involving the Vagus Nerve

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