Mitohormesis in Hypothalamic POMC Neurons Mediates Regular Exercise-Induced High-Turnover Metabolism.
Mitohormesis in Hypothalamic POMC Neurons Mediates Regular Exercise-Induced High-Turnover Metabolism.
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DOI：
10.1016/j.cmet.2021.01.003
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发表时间：
2021-02-02
期刊：
影响因子：
29
通讯作者：
Kim MS
中科院分区：
文献类型：
--
作者：
Kang GM;Min SH;Lee CH;Kim JY;Lim HS;Choi MJ;Jung SB;Park JW;Kim S;Park CB;Dugu H;Choi JH;Jang WH;Park SE;Cho YM;Kim JG;Kim KG;Choi CS;Kim YB;Lee C;Shong M;Kim MS
低水平的线粒体应激可以促进健康和长寿，这种现象称为有丝分裂。在这里，我们证明了相反的低水平和高水平的线粒体核糖体（mitoribosomal）的压力下丘脑proopiomelanocortin（POMC）神经元的代谢效应。POMC神经元特异性严重线粒体应激由于Crif 1同源缺陷导致小鼠肥胖。相比之下，POMC神经元中Crif 1异源缺陷引起的轻度线粒体应激导致高周转代谢和对肥胖的抵抗。这些代谢益处由远端脂肪组织中增强的产热和线粒体未折叠蛋白反应（UPRmt）介导。在POMC神经元中，部分Crif 1缺陷增加β-内啡肽（β-END）和线粒体DNA编码肽MOTS-c的表达。MOTS-c或β-END的中枢给药重现了Crif 1杂合缺陷小鼠的脂肪表型，表明这些因子是潜在的介质。因此，中等强度的规律性跑步运动可刺激下丘脑MOTS-c/β-END表达，诱导脂肪组织UPRmt和产热。我们的研究结果表明，POMC神经元有丝分裂可能是运动诱导的高周转代谢的基础。Kang等人证明，POMC产生神经元中的高水平线粒体应激导致严重肥胖。相反，相同神经元中的低水平线粒体应激增强脂肪组织中的产热，并通过脑和脂肪组织之间的器官间线粒体应激反应来防止肥胖。
Low-grade mitochondrial stress can promote health and longevity, a phenomenon termed mitohormesis. Here, we demonstrate the opposing metabolic effects of low-level and high-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 caused by Crif1 heterodeficiency in POMC neurons leads to high-turnover metabolism and resistance to obesity. These metabolic benefits are mediated by enhanced thermogenesis and mitochondrial unfolded protein responses (UPRmt) in distal adipose tissues. In POMC neurons, partial Crif1 deficiency increases the expression of β-endorphin (β-END) and mitochondrial DNA-encoded peptide MOTS-c. Central administration of MOTS-c or β-END recapitulates the adipose phenotype of Crif1 heterodeficient mice, suggesting these factors as potential mediators. Consistently, regular running exercise at moderate intensity stimulates hypothalamic MOTS-c/β-END expression and induces adipose tissue UPRmt and thermogenesis. Our findings indicate that POMC neuronal mitohormesis may underlie exercise-induced high-turnover metabolism. Kang et al. demonstrate that high-level mitochondrial stress in POMC-producing neurons causes severe obesity. In contrast, low-level mitochondrial stress in the same neurons enhances thermogenesis in the adipose tissue and protects against obesity via interorgan mitochondrial stress responses between the brain and adipose tissue.
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影响因子：
82.9
作者：
Gammage PA;Viscomi C;Simard ML;Costa ASH;Gaude E;Powell CA;Van Haute L;McCann BJ;Rebelo-Guiomar P;Cerutti R;Zhang L;Rebar EJ;Zeviani M;Frezza C;Stewart JB;Minczuk M
通讯作者：
Minczuk M
DOI：
10.1038/oby.2012.95
发表时间：
2012-07
期刊：
Obesity (Silver Spring, Md.)
影响因子：
--
作者：
Harris RB
通讯作者：
Harris RB
影响因子：
11.4
作者：
Kwon, Min-chul;Koo, Bon-Kyoung;Kong, Young-Yun
通讯作者：
Kong, Young-Yun
影响因子：
29
作者：
Chao PT;Yang L;Aja S;Moran TH;Bi S
通讯作者：
Bi S
影响因子：
64.5
作者：
Dodd GT;Decherf S;Loh K;Simonds SE;Wiede F;Balland E;Merry TL;Münzberg H;Zhang ZY;Kahn BB;Neel BG;Bence KK;Andrews ZB;Cowley MA;Tiganis T
通讯作者：
Tiganis T