MicroRNA-378 controls classical brown fat expansion to counteract obesity

نویسندگان

  • Dongning Pan
  • Chunxiao Mao
  • Brian Quattrochi
  • Randall H Friedline
  • Lihua J Zhu
  • Dae Young Jung
  • Jason K Kim
  • Brian Lewis
  • Yong-Xu Wang
چکیده

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.

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عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2014