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研究揭示下丘脑POMC神经元如何调控运动引起的高效代谢
作者:小柯机器人 发布时间:2021/2/5 13:24:48

韩国蔚山大学医学院Min-Seon Kim等研究人员合作发现,下丘脑POMC神经元的线粒体低毒兴奋效应介导规律运动引起的高效代谢。该项研究成果发表在2021年2月2日出版的《细胞—代谢》杂志上。

研究人员证明了下丘脑原核黑素皮质激素(POMC)神经元中低水平和高水平线粒体核糖体应激的相反代谢作用。由于Crif1同源缺失导致的POMC神经元特异性严重线粒体应激导致小鼠肥胖。相比之下,POMC神经元中由Crif1杂合缺失引起的轻度线粒体压力导致高效率的代谢以及对肥胖的抵抗。这些代谢益处是由远端脂肪组织中增强的产热作用和线粒体未折叠蛋白反应(UPRmt)介导的。

在POMC神经元中,Crif1的部分缺乏会增加β-内啡肽(β-END)和线粒体DNA编码的多肽MOTS-c表达。MOTS-c或β-END的中枢给药可重现Crif1杂合缺失小鼠的脂肪表型,从而提示这些因素可能是潜在的介导因素。同样地,以中等强度进行定期跑步锻炼会刺激下丘脑MOTS-c/β-END的表达并诱导脂肪组织UPRmt和产热作用。这些发现表明,POMC神经元的线粒体低毒兴奋效应可能是运动引发高效代谢的基础。 

据了解,轻度的线粒体压力可以促进健康和长寿,这种现象被称为线粒体低毒兴奋效应。

附:英文原文

Title: Mitohormesis in Hypothalamic POMC Neurons Mediates Regular Exercise-Induced High-Turnover Metabolism

Author: Gil Myoung Kang, Se Hee Min, Chan Hee Lee, Ji Ye Kim, Hyo Sun Lim, Min Jeong Choi, Saet-Byel Jung, Jae Woo Park, Seongjun Kim, Chae Beom Park, Hong Dugu, Jong Han Choi, Won Hee Jang, Se Eun Park, Young Min Cho, Jae Geun Kim, Kyung-Gon Kim, Cheol Soo Choi, Young-Bum Kim, Changhan Lee, Minho Shong, Min-Seon Kim

Issue&Volume: 2021/02/02

Abstract: Low-grade mitochondrial stress can promote health and longevity, a phenomenon termedmitohormesis. Here, we demonstrate the opposing metabolic effects of low-level andhigh-level mitochondrial ribosomal (mitoribosomal) stress in hypothalamic proopiomelanocortin(POMC) neurons. POMC neuron-specific severe mitoribosomal stress due to Crif1 homodeficiency causes obesity in mice. By contrast, mild mitoribosomal stress causedby Crif1 heterodeficiency in POMC neurons leads to high-turnover metabolism and resistanceto obesity. These metabolic benefits are mediated by enhanced thermogenesis and mitochondrialunfolded protein responses (UPRmt) in distal adipose tissues. In POMC neurons, partial Crif1 deficiency increases the expression of β-endorphin (β-END) and mitochondrial DNA-encodedpeptide MOTS-c. Central administration of MOTS-c or β-END recapitulates the adiposephenotype of Crif1 heterodeficient mice, suggesting these factors as potential mediators. Consistently,regular running exercise at moderate intensity stimulates hypothalamic MOTS-c/β-ENDexpression and induces adipose tissue UPRmt and thermogenesis. Our findings indicate that POMC neuronal mitohormesis may underlieexercise-induced high-turnover metabolism.

DOI: 10.1016/j.cmet.2021.01.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00003-6

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx