期刊
EMBO REPORTS
卷 22, 期 5, 页码 -出版社
WILEY
DOI: 10.15252/embr.202052146
关键词
adipogenesis; ALKBH5; curcumin; m(6)A; obesity
资金
- National Key RD Program [2018YFD0500405]
- Fundamental Research Funds for ZheJiang Provincial Colleges Universities [2019XZZX003-13]
- Key project of Jinhua Science and Technology [2019-2-003]
The study reveals that curcumin prevents obesity by inhibiting adipogenesis through the regulation of m(6)A demethylase AlkB homolog 5 and YTHDF1-mediated TRAF4 expression.
Obesity has become a major health problem that has rapidly prevailed over the past several decades worldwide. Curcumin, a natural polyphenolic compound present in turmeric, has been shown to have a protective effect on against obesity and metabolic diseases. However, its underlying mechanism remains largely unknown. Here, we show that the administration of curcumin significantly prevents HFD-induced obesity and decreases the fat mass of the subcutaneous inguinal WAT (iWAT) and visceral epididymal WAT (eWAT) in mice. Mechanistically, curcumin inhibits adipogenesis by reducing the expression of AlkB homolog 5 (ALKHB5), an m(6)A demethylase, which leads to higher m(6)A-modified TNF receptor-associated factor 4 (TRAF4) mRNA. TRAF4 mRNA with higher m(6)A level is recognized and bound by YTHDF1, leading to enhanced translation of TRAF4. TRAF4, acting as an E3 RING ubiquitin ligase, promotes degradation of adipocyte differentiation regulator PPAR gamma by a ubiquitin-proteasome pathway thereby inhibiting adipogenesis. Thus, m(6)A-dependent TRAF4 expression upregulation by ALKBH5 and YTHDF1 contributes to curcumin-induced obesity prevention. Our findings provide mechanistic insights into how m(6)A is involved in the anti-obesity effect of curcumin.
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