| First Author | Jeon YG | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 940 |
| PubMed ID | 38296968 | Mgi Jnum | J:349296 |
| Mgi Id | MGI:7580029 | Doi | 10.1038/s41467-024-45270-7 |
| Citation | Jeon YG, et al. (2024) Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates. Nat Commun 15(1):940 |
| abstractText | 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 GABPalpha protein elevation by controlling protein stability, which stimulates thermogenic gene expression. Accordingly, BAT-specific Rnf20 suppression potentiates BAT thermogenic activity via GABPalpha 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 GABPalpha, to activate PPARgamma. Together, current findings propose fat depot-specific regulatory mechanisms for temporal activation of adipose thermogenesis. |
