HDAC11 suppresses the thermogenic program of adipose tissue via BRD2

Rushita A. Bagchi, Bradley S. Ferguson, Matthew S. Stratton, Tianjing Hu, Maria A. Cavasin, Lei Sun, Ying Hsi Lin, Dianxin Liu, Pilar Londono, Kunhua Song, Maria F. Pino, Lauren M. Sparks, Steven R. Smith, Philipp E Scherer, Sheila Collins, Edward Seto, Timothy A. McKinsey

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalJCI insight
Volume3
Issue number15
DOIs
StatePublished - Aug 9 2018

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Histone Deacetylases
Adipose Tissue
Brown Adipose Tissue
Obesity
White Adipose Tissue
Epigenomics
Histones
Adrenergic Receptors
Insulin Resistance
Carrier Proteins
Homeostasis
Fats
Liver
Mouse Hdac11 protein

Keywords

  • Adipose tissue
  • Metabolism
  • Transcription

Cite this

Bagchi, R. A., Ferguson, B. S., Stratton, M. S., Hu, T., Cavasin, M. A., Sun, L., ... McKinsey, T. A. (2018). HDAC11 suppresses the thermogenic program of adipose tissue via BRD2. JCI insight, 3(15). https://doi.org/10.1172/jci.insight.120159

HDAC11 suppresses the thermogenic program of adipose tissue via BRD2. / Bagchi, Rushita A.; Ferguson, Bradley S.; Stratton, Matthew S.; Hu, Tianjing; Cavasin, Maria A.; Sun, Lei; Lin, Ying Hsi; Liu, Dianxin; Londono, Pilar; Song, Kunhua; Pino, Maria F.; Sparks, Lauren M.; Smith, Steven R.; Scherer, Philipp E; Collins, Sheila; Seto, Edward; McKinsey, Timothy A.

In: JCI insight, Vol. 3, No. 15, 09.08.2018.

Research output: Contribution to journalArticle

Bagchi, RA, Ferguson, BS, Stratton, MS, Hu, T, Cavasin, MA, Sun, L, Lin, YH, Liu, D, Londono, P, Song, K, Pino, MF, Sparks, LM, Smith, SR, Scherer, PE, Collins, S, Seto, E & McKinsey, TA 2018, 'HDAC11 suppresses the thermogenic program of adipose tissue via BRD2', JCI insight, vol. 3, no. 15. https://doi.org/10.1172/jci.insight.120159
Bagchi RA, Ferguson BS, Stratton MS, Hu T, Cavasin MA, Sun L et al. HDAC11 suppresses the thermogenic program of adipose tissue via BRD2. JCI insight. 2018 Aug 9;3(15). https://doi.org/10.1172/jci.insight.120159
Bagchi, Rushita A. ; Ferguson, Bradley S. ; Stratton, Matthew S. ; Hu, Tianjing ; Cavasin, Maria A. ; Sun, Lei ; Lin, Ying Hsi ; Liu, Dianxin ; Londono, Pilar ; Song, Kunhua ; Pino, Maria F. ; Sparks, Lauren M. ; Smith, Steven R. ; Scherer, Philipp E ; Collins, Sheila ; Seto, Edward ; McKinsey, Timothy A. / HDAC11 suppresses the thermogenic program of adipose tissue via BRD2. In: JCI insight. 2018 ; Vol. 3, No. 15.
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AU - Song, Kunhua

AU - Pino, Maria F.

AU - Sparks, Lauren M.

AU - Smith, Steven R.

AU - Scherer, Philipp E

AU - Collins, Sheila

AU - Seto, Edward

AU - McKinsey, Timothy A.

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AB - 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.

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