产热
泛素连接酶
下调和上调
脂肪生成
脂肪组织
褐色脂肪组织
白色脂肪组织
细胞生物学
脂肪细胞
生物
产热素
PRDM16
泛素
内分泌学
内科学
生物化学
基因
医学
作者
Yong Geun Jeon,Hahn Nahmgoong,Jiyoung Oh,Dabin Lee,Dong Wook Kim,J. Kim,Ye Young Kim,Yul Ji,Ji Seul Han,Sung‐Min Kim,Jee Hyung Sohn,Won Taek Lee,Sun Won Kim,Jeu Park,Jin Young Huh,Kyuri Jo,Je‐Yoel Cho,Jiyoung Park,Jae Bum Kim
标识
DOI:10.1038/s41467-024-45270-7
摘要
In mammals, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) execute sequential thermogenesis to maintain body temperature during cold stimuli. BAT rapidly generates heat through brown adipocyte activation, and further iWAT gradually stimulates beige fat cell differentiation upon prolonged cold challenges. However, fat depot-specific regulatory mechanisms for thermogenic activation of two fat depots are poorly understood. Here, we demonstrate that E3 ubiquitin ligase RNF20 orchestrates adipose thermogenesis with BAT- and iWAT-specific substrates. Upon cold stimuli, BAT RNF20 is rapidly downregulated, resulting in GABPα protein elevation by controlling protein stability, which stimulates thermogenic gene expression. Accordingly, BAT-specific Rnf20 suppression potentiates BAT thermogenic activity via GABPα upregulation. Moreover, upon prolonged cold stimuli, iWAT RNF20 is gradually upregulated to promote de novo beige adipogenesis. Mechanistically, iWAT RNF20 mediates NCoR1 protein degradation, rather than GABPα, to activate PPARγ. Together, current findings propose fat depot-specific regulatory mechanisms for temporal activation of adipose thermogenesis.
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