Brd4 modulates metabolic endotoxemia-induced inflammation by regulating colonic macrophage infiltration in high-fat diet-fed mice.

ABSTRACT: High-fat diet (HFD) induces low-grade chronic inflammation, contributing to obesity and insulin resistance. However, the precise mechanisms triggering obesity-associated metabolic inflammation remain elusive. In this study, we identified epigenetic factor Brd4 as a key player in this process by regulating the expression of Ccr2/Ccr5 in colonic macrophage. Upon 4-week HFD, myeloid-lineage-specific Brd4 deletion (Brd4-CKO) mice showed reduced colonic inflammation and macrophage infiltration with decreased expression of Ccr2 and Ccr5. Mechanistically, Brd4 was recruited by NF-κB to the enhancer regions of Ccr2 and Ccr5, promoting enhancer RNA expression, which facilitated Ccr2/Ccr5 expression and macrophage migration. Furthermore, decreased infiltration of Ccr2/Ccr5-positive colonic macrophag

SUBMITTER: Hu J 

PROVIDER: S-EPMC11682400 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature