title: Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance.
abstract: 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 β3-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.
authors.affiliation: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Chong Wee
authors.initials: CW
authors.lastname: Liew
authors.forename: Jeremie
authors.initials: J
authors.lastname: Boucher
authors.forename: Jit Kong
authors.initials: JK
authors.lastname: Cheong
authors.forename: Cecile
authors.initials: C
authors.lastname: Vernochet
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Koh
authors.forename: Cristina
authors.initials: C
authors.lastname: Mallol
authors.forename: Kristy
authors.initials: K
authors.lastname: Townsend
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Dan
authors.initials: D
authors.lastname: Kawamori
authors.forename: Jiang
authors.initials: J
authors.lastname: Hu
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Tseng
authors.forename: Marc K
authors.initials: MK
authors.lastname: Hellerstein
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Farmer
authors.forename: Laurie
authors.initials: L
authors.lastname: Goodyear
authors.forename: Alessandro
authors.initials: A
authors.lastname: Doria
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Stephen I-Hong
authors.initials: SI
authors.lastname: Hsu
authors.forename: Rohit N
authors.initials: RN
authors.lastname: Kulkarni
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008066:Lipolysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009765:Obesity / Q000517:prevention & control*; D010084:Oxidation-Reduction; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology; D002787:Sterol Esterase / Q000502:physiology; D022722:Thermogenesis; D014157:Transcription Factors / Q000502:physiology*; D000092468:Bromodomain Containing Proteins
chemical_list: D004041:Dietary Fats; D022702:Receptors, Adrenergic, beta-3; D002787:Sterol Esterase; D014157:Transcription Factors; C426827:SERTAD2 protein, human; D000092468:Bromodomain Containing Proteins; C486065:Sertad2 protein, mouse