产热
脂解
脂肪细胞
下调和上调
内科学
脂肪组织
产热素
内分泌学
线粒体
化学
生物
细胞生物学
生物化学
基因
医学
作者
Meng Ding,Yin-jun Ma,Ruo-Qi Du,Wenbai Zhou,Xia Dou,Qiqi Yang,Yan Tang,Shuwen Qian,Yun Liu,Dongning Pan,Qi‐Qun Tang,Yang Liu
出处
期刊:Diabetes
[American Diabetes Association]
日期:2022-06-16
卷期号:71 (9): 1862-1879
被引量:10
摘要
Brown and beige adipocytes dissipate energy in a nonshivering thermogenesis manner, exerting beneficial effects on metabolic homeostasis. CHCHD10 is a nuclear-encoded mitochondrial protein involved in cristae organization; however, its role in thermogenic adipocytes remains unknown. We identify CHCHD10 as a novel regulator for adipocyte thermogenesis. CHCHD10 is dramatically upregulated during thermogenic adipocyte activation by PPARγ-PGC1α and positively correlated with UCP1 expression in adipose tissues from humans and mice. We generated adipocyte-specific Chchd10 knockout mice (Chchd10-AKO) and found that depleting CHCHD10 leads to impaired UCP1-dependent thermogenesis and energy expenditure in the fasting state, with no effect in the fed state. Lipolysis in adipocytes is disrupted by CHCHD10 deficiency, while augmented lipolysis through ATGL overexpression recovers adipocyte thermogenesis in Chchd10-AKO mice. Consistently, overexpression of Chchd10 activates thermogenic adipocytes. Mechanistically, CHCHD10 deficiency results in the disorganization of mitochondrial cristae, leading to impairment of oxidative phosphorylation complex assembly in mitochondria, which in turn inhibits ATP generation. Decreased ATP results in downregulation of lipolysis by reducing nascent protein synthesis of ATGL, thereby suppressing adipocyte thermogenesis. As a result, Chchd10-AKO mice are prone to develop high-fat diet–induced metabolic disorders. Together, our findings reveal an essential role of CHCHD10 in regulating lipolysis and the thermogenic program in adipocytes.
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