Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance

作者：Liew Chong Wee; Boucher Jeremie; Cheong Jit Kong; Vernochet Cecile; Koh Ho Jin; Mallol Cristina; Townsend Kristy; Langin Dominique; Kawamori Dan; Hu Jiang; Tseng Yu Hua; Hellerstein Marc K; Farmer Stephen R; Goodyear Laurie; Doria Alessandro; Blueher Matthias; Hsu Stephen I Hong; Kulkarni Rohit N^*

来源：Nature Medicine, 2013, 19(2): 217-226.

DOI：10.1038/nm.3056

Obesity develops as a result of altered energy homeostasis favoring fat storage. Here we describe a new transcription co-regulator for adiposity and energy metabolism, SERTA domain containing 2 (TRIP-Br2, also called SERTAD2). TRIP-Br2 null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of these knockout mice showed greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and beta 3-adrenergic (Adrb3) receptors. The knockout mice also have higher energy expenditure because of increased adipocyte thermogenesis and oxidative metabolism caused by upregulating key enzymes in their respective processes. Our data show 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 new therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia.

• 出版日期2013-2