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

Yong Geun Jeon, Hahn Nahmgoong, Jiyoung Oh, Dabin Lee, Dong Wook Kim, Jane Eunsoo 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 and Jae Bum Kim ()
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Yong Geun Jeon: Seoul National University
Hahn Nahmgoong: Seoul National University
Jiyoung Oh: Ulsan National Institute of Science and Technology
Dabin Lee: Seoul National University
Dong Wook Kim: Seoul National University
Jane Eunsoo Kim: Seoul National University
Ye Young Kim: Seoul National University
Yul Ji: Seoul National University
Ji Seul Han: Seoul National University
Sung Min Kim: Seoul National University
Jee Hyung Sohn: Seoul National University
Won Taek Lee: Seoul National University
Sun Won Kim: Seoul National University
Jeu Park: Seoul National University
Jin Young Huh: Seoul National University
Kyuri Jo: Chungbuk National University
Je-Yoel Cho: Seoul National University
Jiyoung Park: Ulsan National Institute of Science and Technology
Jae Bum Kim: Seoul National University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-45270-7

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