| First Author | Mori M | Year | 2012 |
| Journal | PLoS Biol | Volume | 10 |
| Issue | 4 | Pages | e1001314 |
| PubMed ID | 22545021 | Mgi Jnum | J:184796 |
| Mgi Id | MGI:5426327 | Doi | 10.1371/journal.pbio.1001314 |
| Citation | Mori M, et al. (2012) Essential role for miR-196a in brown adipogenesis of white fat progenitor cells. PLoS Biol 10(4):e1001314 |
| abstractText | The recent discovery of functional brown adipocytes in adult humans illuminates the potential of these cells in the treatment of obesity and its associated diseases. In rodents, brown adipocyte-like cells are known to be recruited in white adipose tissue (WAT) by cold exposure or beta-adrenergic stimulation, but the molecular machinery underlying this phenomenon is not fully understood. Here, we show that inducible brown adipogenesis is mediated by the microRNA miR-196a. We found that miR-196a suppresses the expression of the white-fat gene Hoxc8 post-transcriptionally during the brown adipogenesis of white fat progenitor cells. In mice, miR-196a is induced in the WAT-progenitor cells after cold exposure or beta-adrenergic stimulation. The fat-specific forced expression of miR-196a in mice induces the recruitment of brown adipocyte-like cells in WAT. The miR-196a transgenic mice exhibit enhanced energy expenditure and resistance to obesity, indicating the induced brown adipocyte-like cells are metabolically functional. Mechanistically, Hoxc8 targets and represses C/EBPbeta, a master switch of brown-fat gene program, in cooperation with histone deacetylase 3 (HDAC3) through the C/EBPbeta 3' regulatory sequence. Thus, miR-196a induces functional brown adipocytes in WAT through the suppression of Hoxc8, which functions as a gatekeeper of the inducible brown adipogenesis. The miR-196a-Hoxc8-C/EBPbeta signaling pathway may be a therapeutic target for inducing brown adipogenesis to combat obesity and type 2 diabetes. |
