title: Role of histone deacetylase 9 in regulating adipogenic differentiation and high fat diet-induced metabolic disease.
abstract: Adipose 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.
authors: Department of Internal Medicine; Vascular Biology Center; Georgia Regents University ; Augusta, GA USA.
authors: Tapan K
authors: TK
authors: Chatterjee
authors: Department of Pathology; Metabolic Disease Institute; University of Cincinnati ; Cincinnati, OH USA.
authors: Joshua E
authors: JE
authors: Basford
authors: Department of Pharmacology; Vascular Biology Center; Georgia Regents University ; Augusta, GA USA.
authors: Kan Hui
authors: KH
authors: Yiew
authors: Department of Physiology; Vascular Biology Center; Georgia Regents University ; Augusta, GA USA.
authors: David W
authors: DW
authors: Stepp
authors: Department of Pathology; Metabolic Disease Institute; University of Cincinnati ; Cincinnati, OH USA.
authors: David Y
authors: DY
authors: Hui
authors: Department of Internal Medicine; Vascular Biology Center; Georgia Regents University ; Augusta, GA USA.
authors: Neal L
authors: NL
authors: Weintraub
keywords: 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