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

Nat Med. 2013 Feb;19(2):217-26. doi: 10.1038/nm.3056. Epub 2013 Jan 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / pathology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Dietary Fats / administration & dosage
  • Female
  • Humans
  • Insulin Resistance*
  • Lipolysis*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Obesity / prevention & control*
  • Oxidation-Reduction
  • Receptors, Adrenergic, beta-3 / physiology
  • Sterol Esterase / physiology
  • Thermogenesis*
  • Transcription Factors / physiology*


  • Dietary Fats
  • Receptors, Adrenergic, beta-3
  • SERTAD2 protein, human
  • Sertad2 protein, mouse
  • Transcription Factors
  • Sterol Esterase