HDAC11 suppresses the thermogenic program of adipose tissue via BRD2

JCI Insight. 2018 Aug 9;3(15):e120159. doi: 10.1172/jci.insight.120159.


Little is known about the biological function of histone deacetylase 11 (HDAC11), which is the lone class IV HDAC. Here, we demonstrate that deletion of HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT). Consequently, HDAC11-deficient mice exhibit enhanced thermogenic potential and, in response to high-fat feeding, attenuated obesity, improved insulin sensitivity, and reduced hepatic steatosis. Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone-binding protein. These findings define an epigenetic pathway for the regulation of energy homeostasis and suggest the potential for HDAC11-selective inhibitors for the treatment of obesity and diabetes.

Keywords: Adipose tissue; Metabolism; Transcription.

Publication types

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

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, Brown / pathology
  • Adipose Tissue, White / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Energy Metabolism / genetics
  • Epigenesis, Genetic / physiology
  • Fatty Liver / genetics
  • Fatty Liver / pathology*
  • Female
  • Gene Expression Regulation / physiology
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Insulin Resistance / genetics
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Obesity / genetics
  • Obesity / pathology*
  • Thermogenesis / genetics*
  • Transcription Factors / metabolism*


  • BRD2 protein, human
  • Brd2 protein, mouse
  • Transcription Factors
  • HDAC11 protein, human
  • Hdac11 protein, mouse
  • Histone Deacetylases