POMC neurons expressing leptin receptors coordinate metabolic responses to fasting via suppression of leptin levels
- University of Texas Southwestern Medical Center, United States
- Howard Community College, United States
- University of Texas Health Science Center at San Antonio, United States
Abstract
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 controlled Lepr expression 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.
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Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R37DK053301)
- Joel K Elmquist
Canadian Diabetes Association (NOD_PF-3-15-4756-AC)
- Alexandre Caron
American Heart Association (14SDG17950008)
- Teppei Fujikawa
National Institute of Diabetes and Digestive and Kidney Diseases (K01DK11164401)
- Carlos M Castorena
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK114036)
- Chen Liu
American Heart Association (16SDG27260001)
- Chen Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal work described in this manuscript has been approved and conducted under the oversight of the UT Southwestern Institutional Animal Care and Use Committee (IACUC, APN 2015-101301 and APN 2015-101263).
Copyright
© 2018, Caron et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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POMC neurons expressing leptin receptors coordinate metabolic responses to fasting via suppression of leptin levels
eLife 7:e33710.
https://doi.org/10.7554/eLife.33710
