POMC neurons expressing leptin receptors coordinate metabolic responses to fasting via suppression of leptin levels.
POMC neurons expressing leptin receptors coordinate metabolic responses to fasting via suppression of leptin levels.
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DOI：
10.7554/elife.33710
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发表时间：
2018-03-12
期刊：
影响因子：
7.7
通讯作者：
Elmquist JK
中科院分区：
文献类型：
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作者：
Caron A;Dungan Lemko HM;Castorena CM;Fujikawa T;Lee S;Lord CC;Ahmed N;Lee CE;Holland WL;Liu C;Elmquist JK
瘦素对能量平衡、葡萄糖稳态以及对饥饿的代谢和神经内分泌适应至关重要。流行的模型预测瘦素的作用是通过表达瘦素受体（LEPR）的前阿黑皮素（POMC）神经元介导的。然而，之前的研究使用了产前基因操作，这可能会受到发育补偿的影响。在这里，我们测试的直接贡献POMC神经元表达LEPR在调节能量平衡，葡萄糖稳态和瘦素分泌在禁食期间使用时空控制的Lepr表达小鼠模型。我们报道了瘦素对POMC神经元葡萄糖稳态与能量平衡的影响之间的分离。我们发现，这些神经元是调节食物摄入，但需要协调肝葡萄糖的生产和空腹诱导的瘦素水平下降，独立于脂肪量的变化。我们还确定了交感神经系统调节抑制性肾上腺素能受体（ADRA 2A）在调节瘦素产生的作用。总的来说，我们的研究结果强调了以前未被认识的作用，POMC神经元在调节瘦素水平。
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.