POMC neurons expressing leptin receptors coordinate metabolic responses to fasting via suppression of leptin levels
Autor: | Carlos M. Castorena, Heather M Dungan Lemko, Alexandre Caron, Syann Lee, Newaz Ahmed, Chen Liu, Charlotte E. Lee, Caleb C. Lord, Joel K. Elmquist, William L. Holland, Teppei Fujikawa |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Food intake Sympathetic nervous system Pro-Opiomelanocortin Sympathetic Nervous System Mouse Glucose homeostasis Eating Mice Homeostasis Biology (General) Neurons General Neuroscience Leptin digestive oral and skin physiology POMC General Medicine medicine.anatomical_structure Receptors Leptin Medicine hormones hormone substitutes and hormone antagonists Research Article medicine.medical_specialty Adrenergic receptor fasting QH301-705.5 Science Biology Inhibitory postsynaptic potential ADRA2A leptin General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Receptors Adrenergic alpha-2 Internal medicine medicine Animals Humans Secretion Human Biology and Medicine Leptin receptor General Immunology and Microbiology 030104 developmental biology Endocrinology Glucose nervous system Energy Metabolism Neuroscience |
Zdroj: | eLife, Vol 7 (2018) eLife |
Popis: | Leptin is critical for energy balance, glucose homeostasis, and for metabolic and neuroendocrine adaptations to starvation. A prevalent model predicts that leptin’s actions are mediated through pro-opiomelanocortin (POMC) neurons that express leptin receptors (LEPRs). However, previous studies have used prenatal genetic manipulations, which may be subject to developmental compensation. Here, we tested the direct contribution of POMC neurons expressing LEPRs in regulating energy balance, glucose homeostasis and leptin secretion during fasting using a spatiotemporally controlledLeprexpression mouse model. We report a dissociation between leptin’s effects on glucose homeostasis versus energy balance in POMC neurons. We show that these neurons are dispensable for regulating food intake, but are required for coordinating hepatic glucose production and for the fasting-induced fall in leptin levels, independent of changes in fat mass. We also identify a role for sympathetic nervous system regulation of the inhibitory adrenergic receptor (ADRA2A) in regulating leptin production. Collectively, our findings highlight a previously unrecognized role of POMC neurons in regulating leptin levels. |
Databáze: | OpenAIRE |
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