Bromodomain-containing protein 2 induces insulin resistance via the mTOR/Akt signaling pathway and an inflammatory response in adipose tissue

Insulin resistance is a major metabolic abnormality in a large majority of patients with type II diabetes. Bromodomain-containing protein 2 (Brd2), a transcriptional co-activator/co-repressor with switch mating type/sucrose non-fermenting (SWI/SNF)-like functions that regulates chromatin, suppresses adipocyte differentiation and regulates pancreatic β-cell biology. However, the effects of Brd2 on Insulin resistance remain unknown. Here, overexpression of Brd2 in white adipose tissue of wild-type (WT) mice led to Insulin resistance. Brd2 overexpression induced the expression of nuclear Factor-κΒ (NF-κΒ) target genes, mainly involving proinflammatory and chemotactic factors, in adipocytes. Furthermore, it decreased the expression of DEP domain containing mTOR-interacting protein (Deptor) to enhance mechanistic target of rapamycin (mTOR) signaling, thus blocking Insulin signaling. Collectively, these results provided evidence for a novel role of Brd2 in chronic inflammation and Insulin resistance, suggesting its potential in improving Insulin resistance and treating metabolic disorders.

Brd2; Inflammation; Insulin resistance; Insulin signaling pathway; mTOR signaling.