| First Author | Chen M | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 2 | Pages | eaax9605 |
| PubMed ID | 31934629 | Mgi Jnum | J:287138 |
| Mgi Id | MGI:6415422 | Doi | 10.1126/sciadv.aax9605 |
| Citation | Chen M, et al. (2020) CTNNB1/beta-catenin dysfunction contributes to adiposity by regulating the cross-talk of mature adipocytes and preadipocytes. Sci Adv 6(2):eaax9605 |
| abstractText | Overnutrition results in adiposity and chronic inflammation with expansion of white adipose tissue (WAT). However, genetic factors controlling fat mass and adiposity remain largely undetermined. We applied whole-exome sequencing in young obese subjects and identified rare gain-of-function mutations in CTNNB1/beta-catenin associated with increased obesity risk. Specific ablation of beta-catenin in mature adipocytes attenuated high-fat diet-induced obesity and reduced sWAT mass expansion with less proliferated Pdgfralpha(+) preadipocytes and less mature adipocytes. Mechanistically, beta-catenin regulated the transcription of serum amyloid A3 (Saa3), an adipocyte-derived chemokine, through beta-catenin-TCF (T-Cell-Specific Transcription Factor) complex in mature adipocytes, and Saa3 activated macrophages to secrete several factors, including Pdgf-aa, which further promoted the proliferation of preadipocytes, suggesting that beta-catenin/Saa3/macrophages may mediate mature adipocyte-preadipocyte cross-talk and fat expansion in sWAT. The identification of beta-catenin as a key regulator in fat expansion and human adiposity provides the basis for developing drugs targeting Wnt/beta-catenin pathway to combat obesity. |
