Role of histone deacetylase 9 in regulating adipogenic differentiation and high fat diet-induced metabolic disease

Tapan K. Chatterjee, Joshua E. Basford, Kan Hui Yiew, David W. Stepp, David Y. Hui, Neal L. Weintraub

Research output: Contribution to journalComment/debatepeer-review

24 Scopus citations


A dipose tissue serves as both a storage site for excess calories and as an endocrine organ, secreting hormones such as adiponectin that promote metabolic homeostasis. In obesity, adipose tissue expands primarily by hypertrophy (enlargement of existing adipocytes) rather than hyperplasia (generation of new adipocytes via adipogenic differentiation of preadipocytes). Progressive adipocyte hypertrophy leads to inflammation, insulin resistance, dyslipidemia, and ectopic lipid deposition, the hallmark characteristics of metabolic disease. We demonstrate that during chronic high fat feeding in mice, adipogenic differentiation is impaired due to the actions of histone deacetylase 9 (HDAC9), a member of the class II family of HDACs. Mechanistically, upregulated HDAC9 expression blocks the adipogenic differentiation program during chronic high fat feeding, leading to accumulation of improperly differentiated adipocytes with diminished expression of adiponectin. These adipocytes are inefficient at storing lipid, resulting in ectopic lipid deposition in the liver. HDAC9 gene deletion prevents the detrimental effects of chronic high fat feeding on adipogenic differentiation, increases adiponectin expression, and enhances energy expenditure by promoting beige adipogenesis, thus leading to reduced body mass and improved metabolic homeostasis. HDAC9 is therefore emerging as a critical regulator of adipose tissue health and a novel therapeutic target for obesity-related disease.

Original languageEnglish (US)
Pages (from-to)333-338
Number of pages6
Issue number4
StatePublished - 2014
Externally publishedYes


  • Adaptive thermogenesis
  • Adipogenic differentiation
  • Adipose tissue dysfunction
  • Beige adipocytes
  • Ectopic lipid accumulation
  • Energy expenditure
  • Fibroblast growth factor 21
  • Glucose intolerance
  • High fat diet
  • Histone deacetylase 9
  • Insulin resistance
  • Metabolic disease
  • Obesity

ASJC Scopus subject areas

  • Histology
  • Cell Biology


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