Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis
Autor: | Chen Liu, Jong Woo Sohn, Eric D. Berglund, Kevin W. Williams, Yong Xu, Tiemin Liu, Mi Hwa Kim, Claudia R. Vianna, Joel K. Elmquist, Charlotte E. Lee |
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Rok vydání: | 2014 |
Předmět: |
Male
medicine.medical_specialty endocrine system Serotonin Pro-Opiomelanocortin Recombinant Fusion Proteins Drug Resistance Biology Hyperphagia Serotonergic Mice Insulin resistance Dietary Sucrose Internal medicine Hyperinsulinism Appetite Depressants Insulin Secretion medicine Receptor Serotonin 5-HT2C Glucose homeostasis Animals Homeostasis Insulin Obesity Receptor 5-HT receptor Mice Knockout Neurons Body Weight Feeding Behavior General Medicine medicine.disease Glucagon Dietary Fats Serotonin Receptor Agonists Endocrinology Glucose nervous system Hypothalamus Hyperglycemia Female Insulin Resistance Energy Metabolism Corrigendum hormones hormone substitutes and hormone antagonists Research Article |
Zdroj: | Journal of Clinical Investigation. 124:1868-1868 |
ISSN: | 0021-9738 |
Popis: | Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control. |
Databáze: | OpenAIRE |
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