Abstract
White adipose tissue (WAT) dysfunction is prevalent among patients with type 2 diabetes mellitus (T2DM). Uncontrolled free fatty acid (FFA) release from WAT stores has detrimental effects on lipid metabolism, leading to insulin resistance. Bromodomain-containing protein 2 (Brd2) has emerged as a central transcriptional regulator of adipocyte differentiation and pancreatic β-cell bioactivity. A recent study shows that Brd2 overexpression leads to insulin resistance in mice. However, the mechanisms underlying these effects have not been fully elucidated. This study provides the first evidence that adenoviral-mediated Brd2 overexpression in the WAT of mice increases lipolysis-related gene expression in addition to significantly reducing WAT size and promoting plasma FFA release. Brd2 overexpression in adipocytes also inhibits fat synthesis-related gene expression, while activating hormone-sensitive lipase (HSL) expression and ERK-dependent perilipin 1 inhibition as well as promoting glycerol release, which are all involved in lipolysis. Collectively, these results indicate that Brd2 triggers insulin resistance via lipolysis-mediated FFA release.