MicroRNA-378 controls classical brown fat expansion to counteract obesity
Program in Gene Function and Expression; Program in Molecular Medicine
Cellular and Molecular Physiology | Molecular Biology | Molecular Genetics
Both classical brown adipocytes and brown-like beige adipocytes are considered as promising therapeutic targets for obesity; however, their development, relative importance and functional coordination are not well understood. Here we show that a modest expression of miR-378/378* in adipose tissue specifically increases classical brown fat (BAT) mass, but not white fat (WAT) mass. Remarkably, BAT expansion, rather than miR-378 per se, suppresses formation of beige adipocytes in subcutaneous WAT. Despite this negative feedback, the expanded BAT depot is sufficient to prevent both genetic and high-fat diet-induced obesity. At the molecular level, we find that miR-378 targets phosphodiesterase Pde1b in BAT but not in WAT. Indeed, miR-378 and Pde1b inversely regulate brown adipogenesis in vitro in the absence of phosphodiesterase inhibitor isobutylmethylxanthine. Our work identifies miR-378 as a key regulatory component underlying classical BAT-specific expansion and obesity resistance, and adds novel insights into the physiological crosstalk between BAT and WAT.
DOI of Published Version
Nat Commun. 2014 Aug 22;5:4725. doi: 10.1038/ncomms5725. Link to article on publisher's site
Pan, Dongning; Mao, Chunxiao; Quattrochi, Brian; Friedline, Randall H.; Zhu, Lihua Julie; Jung, Dae Young; Kim, Jason K.; Lewis, Brian C.; and Wang, Yong-Xu, "MicroRNA-378 controls classical brown fat expansion to counteract obesity" (2014). Program in Gene Function and Expression Publications and Presentations. 264.