Histone deacetylase 1 plays an important role in brown adipogenesis (817.4)

Abstract

Induction of brown adipocytes in white fat plays an important role in the regulation of energy homeostasis. Here, we have investigated the role of HDAC1 in brown adipogenesis. The RNA and protein levels of HDAC1 are lower in mice brown compared to white adipose tissue, in brown adipose tissue of mice exposed to cold compared to that of mice residing in room temperature, and reduced during brown adipocyte differentiation. Overexpression of HDAC1 inhibits, whereas genetic deletion of HDAC1 results in further enhancement of isoproterenol‐stimulated expression of uncoupling protein 1 (UCP1) and other BAT‐specific genes, including peroxisome proliferative activated receptor γ coactivator 1α (PGC1α), PGC1β, PR domain containing 16 (PRDM16), type 2 deiodinase (DIO2), fibroblast growth factor 21 (FGF21) and myelin protein zero‐like 2 (Eva1) in brown adipocyte cell lines BAT‐1 and HIB1B. Chromatin immunoprecipitation assay indicates that histone H3 and H4 acetylation is significantly increased at the UCP1 promoter in β‐adrenergic stimulated brown adipocytes, which is also associated with increased active histone markers H3 lysine 4 tri‐methylation, and H3 lysine 27 acetylation. Thus, our data suggest that epigenetics plays an important role in brown adipogenesis and thermogenesis, and identify HDAC1 as an important regulator during this process.Grant Funding Source: NIHR01HL107500