| First Author | Zhang W | Year | 2020 |
| Journal | Diabetes | Volume | 69 |
| Issue | 12 | Pages | 2642-2654 |
| PubMed ID | 32994276 | Mgi Jnum | J:300589 |
| Mgi Id | MGI:6502773 | Doi | 10.2337/db20-0437 |
| Citation | Zhang W, et al. (2020) Muscular G9a Regulates Muscle-Liver-Fat Axis by Musclin Under Overnutrition in Female Mice. Diabetes 69(12):2642-2654 |
| abstractText | Cross talk among different tissues and organs is a hotspot in metabolic research. Recent studies have revealed the regulatory roles of a number of myokines in metabolism. Here, we report that female mice lacking muscle-specific histone methylase G9a (Ehmt2 (Ckmm) knockout [KO] or Ehmt2 (HSA) KO) are resistant to high-fat diet (HFD)-induced obesity and hepatic steatosis. Furthermore, we identified a significantly upregulated circulating level of musclin, a myokine, in HFD-fed Ehmt2 (Ckmm) KO or Ehmt2 (HSA) KO female mice. Similarly, upregulated musclin was observed in mice injected with two structurally different inhibitors for G9a methylase activity: BIX01294 and A366. Moreover, injection of recombinant full-length musclin or its functional core domain inhibited the HFD-induced obesity and hepatic steatosis in wild-type female and male mice. Mechanistically, G9a methylase activity-dependently regulated muscular musclin level by binding to its promoter, also by regulating phosphorylated-FOXO1/FOXO1 levels in vivo and in vitro. Collectively, these data suggest a critical role for G9a in the muscle-liver-fat metabolic axis, at least for female mice. Musclin may serve as a potential therapeutic candidate for obesity and associated diseases. |
