An adipokine feedback regulating diurnal food intake rhythms in mice
An adipokine feedback regulating diurnal food intake rhythms in mice
复制标题
DOI：
10.7554/elife.55388
复制
发表时间：
2020-07-09
期刊：
影响因子：
7.7
通讯作者：
Oster, Henrik
中科院分区：
文献类型：
--
作者：
Tsang, Anthony H.;Koch, Christiane E.;Oster, Henrik
内源性生物钟已经进化到可以预测环境需求中的24小时节律。最近的研究表明，昼夜节律紊乱是人类代谢紊乱发展的主要危险因素。相反，能量状态的改变会扰乱行为和生理的昼夜节律，造成代谢功能障碍的恶性循环。然而，外周能量状态如何影响昼夜食物摄入量仍然知之甚少。我们在这里表明，脂肪因子脂联素（ADIPOQ）调节昼夜摄食节律，通过时钟的能量调节中心的中基底下丘脑（MBH）。Adipoq缺乏小鼠表现出与MBH中时钟和食欲调节基因的转录节律中断相关的休息期食物摄入增加。ADIPOQ通过AdipoRl介导的核心时钟基因Bmall的上调来调节MBH时钟。BMAL1反过来控制MBH中食欲神经肽的表达。总之，这些数据揭示了一个系统的代谢回路，以调节中央生物钟和能量摄入。
Endogenous circadian clocks have evolved to anticipate 24 hr rhythms in environmental demands. Recent studies suggest that circadian rhythm disruption is a major risk factor for the development of metabolic disorders in humans. Conversely, alterations in energy state can disrupt circadian rhythms of behavior and physiology, creating a vicious circle of metabolic dysfunction. How peripheral energy state affects diurnal food intake, however, is still poorly understood. We here show that the adipokine adiponectin (ADIPOQ) regulates diurnal feeding rhythms through clocks in energy regulatory centers of the mediobasal hypothalamus (MBH). Adipoq-deficient mice show increased rest phase food intake associated with disrupted transcript rhythms of clock and appetite-regulating genes in the MBH. ADIPOQ regulates MBH clocks via AdipoRl-mediated upregulation of the core clock gene Bmal1. BMAL1, in turn, controls expression of orexigenic neuropeptide expression in the MBH. Together, these data reveal a systemic metabolic circuit to regulate central circadian clocks and energy intake.