Reference - Detail
| 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 |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | pGL3-mUcp1Enhancer_MiniPromoter_Luciferase (RDB20463) pGL3-mPgc1aEnhancer_MiniPromoter_Luciferase (RDB20464) pGL3-mMtif2Promoter_Luciferase (RDB20465) |