| RRC ID |
82642
|
| Author |
Jeon YG, Nahmgoong H, Oh J, Lee D, Kim DW, Kim JE, Kim YY, Ji Y, Han JS, Kim SM, Sohn JH, Lee WT, Kim SW, Park J, Huh JY, Jo K, Cho JY, Park J, Kim JB.
|
| Title |
Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates.
|
| Journal |
Nat Commun
|
| 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.
|
| Volume |
15(1)
|
| Pages |
940
|
| Published |
2024-1-31
|
| DOI |
10.1038/s41467-024-45270-7
|
| PII |
10.1038/s41467-024-45270-7
|
| PMID |
38296968
|
| PMC |
PMC10831072
|
| MeSH |
Adipocytes, Brown / metabolism
Adipose Tissue, Beige* / metabolism
Adipose Tissue, Brown* / metabolism
Adipose Tissue, White / metabolism
Animals
Cold Temperature
Humans
Ligases / metabolism
Mammals
Mice
Mice, Inbred C57BL
Obesity / metabolism
Thermogenesis
Ubiquitin / metabolism
Ubiquitin-Protein Ligases* / genetics
Ubiquitin-Protein Ligases* / metabolism
|
| Resource |
| DNA material |
pGL3-mUcp1Enhancer_MiniPromoter_Luciferase (RDB20463)
pGL3-mPgc1aEnhancer_MiniPromoter_Luciferase (RDB20464)
pGL3-mMtif2Promoter_Luciferase (RDB20465) |
