Liew, Chong WeeBoucher, JeremieCheong, Jit KongVernochet, CecileKoh, Ho-JinMallol, CristinaTownsend, Kristy LLangin, DominiqueKawamori, DanHu, JiangTseng, Yu-HuaHellerstein, Marc KFarmer, Stephen RGoodyear, LaurieDoria, AlessandroBlüher, MatthiasHsu, Stephen I-HongKulkarni, Rohit2014-03-012012Liew, C. W., J. Boucher, J. K. Cheong, C. Vernochet, H. Koh, C. Mallol, K. Townsend, et al. 2012. “Ablation of TRIP-Br2, a novel regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance.” Nature medicine 19 (2): 217-226. doi:10.1038/nm.3056. http://dx.doi.org/10.1038/nm.3056.1078-8956http://nrs.harvard.edu/urn-3:HUL.InstRepos:11855751SUMMARY Obesity develops due to altered energy homeostasis favoring fat storage. Here we describe a novel transcription co-regulator for adiposity and energy metabolism, TRIP-Br2 (also called SERTAD2). TRIP-Br2 null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of the knockout (KO) mice exhibited greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and β3-adrenergic (Adrb3) receptors. The KOs also exhibit higher energy expenditure due to increased adipocyte thermogenesis and oxidative metabolism by up-regulating key enzymes in respective processes. Our data show for the first time that a cell cycle transcriptional co-regulator, TRIP-Br2, modulates fat storage through simultaneous regulation of lipolysis, thermogenesis and oxidative metabolism. These data together with the observation that TRIP-BR2 expression is selectively elevated in visceral fat in obese humans suggests that this transcriptional co-regulator is a novel therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia.en-USJournal Article2014-03-0110.1038/nm.3056