Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates

Author:

Jeon Yong GeunORCID,Nahmgoong Hahn,Oh Jiyoung,Lee Dabin,Kim Dong Wook,Kim Jane Eunsoo,Kim Ye YoungORCID,Ji Yul,Han Ji SeulORCID,Kim Sung Min,Sohn Jee Hyung,Lee Won TaekORCID,Kim Sun WonORCID,Park Jeu,Huh Jin Young,Jo KyuriORCID,Cho Je-YoelORCID,Park JiyoungORCID,Kim Jae BumORCID

Abstract

AbstractIn 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.

Funder

National Research Foundation of Korea

Publisher

Springer Science and Business Media LLC

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