小柯机器人

马克斯普朗克代谢研究所Jens Claus Brüning小组发现，营养感应的AgRP神经元在能量匮乏期间对肝脏自噬的控制进行转达。2023年4月18日，《细胞—代谢》杂志在线发表了这项成果。

研究人员发现，小鼠禁食会激活肝脏中的自噬，与下丘脑AgRP神经元的激活平行。AgRP神经元的光遗传学和化学遗传学激活诱导自噬，改变自噬调节器的磷酸化，并促进生酮作用。AgRP神经元对肝脏自噬的诱导依赖于下丘脑室旁核（PVH）的NPY释放，通过突触前抑制表达NPY1R的神经元来激活PVHCRH神经元。相反，在能量匮乏期间抑制AgRP神经元会废除肝脏自噬的诱导和代谢的重构。AgRP神经元的激活会增加循环皮质酮的浓度，而减少肝脏糖皮质激素受体的表达，会减弱AgRP神经元对肝脏自噬的激活。总之，这项研究揭示了肝脏自噬在控制营养匮乏期间的代谢适应方面的一个基本调节原则。

据介绍，在感知能量匮乏时，自噬是衰老和新陈代谢的一个关键调节器。

附：英文原文

Title: Nutrient-sensing AgRP neurons relay control of liver autophagy during energy deprivation

Author: Weiyi Chen, Oliver Mehlkop, Alexandra Scharn, Hendrik Nolte, Paul Klemm, Sinika Henschke, Lukas Steuernagel, Tamara Sotelo-Hitschfeld, Ecem Kaya, Claudia Maria Wunderlich, Thomas Langer, Natalia L. Kononenko, Patrick Giavalisco, Jens Claus Brüning

Issue&Volume: 2023-04-18

Abstract: Autophagy represents a key regulator of aging and metabolism in sensing energy deprivation. We find that fasting in mice activates autophagy in the liver paralleled by activation of hypothalamic AgRP neurons. Optogenetic and chemogenetic activation of AgRP neurons induces autophagy, alters phosphorylation of autophagy regulators, and promotes ketogenesis. AgRP neuron-dependent induction of liver autophagy relies on NPY release in the paraventricular nucleus of the hypothalamus (PVH) via presynaptic inhibition of NPY1R-expressing neurons to activate PVHCRH neurons. Conversely, inhibiting AgRP neurons during energy deprivation abrogates induction of hepatic autophagy and rewiring of metabolism. AgRP neuron activation increases circulating corticosterone concentrations, and reduction of hepatic glucocorticoid receptor expression attenuates AgRP neuron-dependent activation of hepatic autophagy. Collectively, our study reveals a fundamental regulatory principle of liver autophagy in control of metabolic adaptation during nutrient deprivation.

DOI: 10.1016/j.cmet.2023.03.019

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00124-9

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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