BET bromodomain inhibition suppresses adipogenesis in mice

Purpose: We recently reported that inhibition of BET bromodomain suppresses adipogenesis in vitro. In the present study we aimed to address whether BET bromodomain inhibition can suppress adipogenesis in vivo.

Methods: Brd4^fl/fl mice were crossed with B6.Cg-Tg(Fabp4-cre)1Rev/J mice to generate Brd4^fl/+/Fabp4-cre mice. We used high fat diet (HFD, 45% fat) mice treated with vehicle (DMSO) or JQ1 (intraperitoneal, IP injection, 50 mg/kg/day), respectively, for 6 weeks. Body weight was measured once a week. Dual-energy X-ray absorptiometry was determined and brown adipose tissue was harvested at the end of the experiment.

Results: Partial deletion of Brd4 leads to the lower body weight. JQ1 treatment further confirmed that BET bromodomain inhibition suppresses body weight gain and decreases white adipose depots compared with the control mice. In addition, JQ1 treatment reduces the size of brown adipose tissue and impairs its thermogenesis.

Conclusions: BET bromodomain inhibition suppresses adipogenesis in the mice.