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表达瘦素受体的 POMC 神经元通过抑制瘦素水平来协调对禁食的代谢反应。

POMC neurons expressing leptin receptors coordinate metabolic responses to fasting via suppression of leptin levels.

机构信息

Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.

Howard Community College, Columbia, United States.

出版信息

Elife. 2018 Mar 12;7:e33710. doi: 10.7554/eLife.33710.

DOI:10.7554/eLife.33710
PMID:29528284
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5866097/
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 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.

摘要

瘦素对于能量平衡、葡萄糖稳态以及代谢和神经内分泌对饥饿的适应至关重要。一种流行的模型预测，瘦素的作用是通过表达瘦素受体 (LEPR) 的阿黑皮素原 (POMC) 神经元介导的。然而，以前的研究使用了产前基因操作，这可能受到发育补偿的影响。在这里，我们使用时空控制表达的小鼠模型测试了表达 LEPR 的 POMC 神经元在调节禁食期间能量平衡、葡萄糖稳态和瘦素分泌中的直接作用。我们报告了瘦素对葡萄糖稳态与 POMC 神经元能量平衡之间的作用分离。我们表明，这些神经元对于调节食物摄入是可有可无的，但对于协调肝葡萄糖产生和禁食诱导的瘦素水平下降是必需的，而与脂肪量的变化无关。我们还确定了交感神经系统对抑制性肾上腺素能受体 (ADRA2A) 的调节在调节瘦素产生中的作用。总的来说，我们的发现强调了 POMC 神经元在调节瘦素水平方面的先前未被认识到的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/3fb3e812b06b/elife-33710-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/00d4e43e2205/elife-33710-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/75ebe8f6d900/elife-33710-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/70ea8a79698c/elife-33710-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/ca7a1edd1b99/elife-33710-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/2087206398d6/elife-33710-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/a66c942b10e2/elife-33710-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/c3a9c21fe5a4/elife-33710-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/ac7a53d9315d/elife-33710-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/3fb3e812b06b/elife-33710-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/00d4e43e2205/elife-33710-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/75ebe8f6d900/elife-33710-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/70ea8a79698c/elife-33710-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/ca7a1edd1b99/elife-33710-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/2087206398d6/elife-33710-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/a66c942b10e2/elife-33710-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/c3a9c21fe5a4/elife-33710-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/ac7a53d9315d/elife-33710-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/5866097/3fb3e812b06b/elife-33710-fig7.jpg

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