Ablation of TRIP-Br2, a novel regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance
Liew, Chong Wee
Cheong, Jit Kong
Hellerstein, Marc K
Farmer, Stephen R
Hsu, Stephen I-Hong
MetadataShow full item record
CitationLiew, 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.
AbstractSUMMARY 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11855751