BET bromodomain inhibition suppresses adipogenesis in mice
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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.
Brd4fl/fl mice were crossed with B6.Cg-Tg(Fabp4-cre)1Rev/J mice to generate Brd4fl/+/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.
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.
BET bromodomain inhibition suppresses adipogenesis in the mice.
KeywordsBET bromodomain Adipogenesis JQ1 Epigenetics
We thank Xiong Xiao for assistance with image editing and Virangika K. Wimalasena for critical reading and editing of the paper. This work was supported by grants from the National Natural Science Foundation of China 81370320, 81770358, 81570334 (T.Y.), 81770867 (Q.D.), the National Institute of Health in US (NIH) HL-127240 (J.Q.), the Natural Science Foundation of Hunan Province 2017JJ2379 (Q.D.), China Postdoctoral Science Foundation 2017T100612 (Q.D.), and the Zijing Foundation 2014-0016 (Q.D.).
Q.D., P.W., Z.L., F.X., L.Z., performed the studies; Q.D., T.Y., and J.Q. designed the research, analyzed data, and prepared the paper; Q.D., T.Y., Z.Z., and J.Q. contributed to the discussion and supervised the study. All authors read and approved the final version of the paper.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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