BRD2 promotes inflammation and lipid accumulation through the NF-κB pathway in alcoholic liver injury

Alcoholic liver injury (ALI) is a significant global health burden, characterized by hepatic inflammation and metabolic dysfunction. This study revealed a critical role of Bromodomain-containing Protein 2 (BRD2) in regulating macrophage-mediated inflammation during ALI. We demonstrated that BRD2 expression is significantly upregulated in both the liver tissue and primary Kupffer cells following ALI. Adenovirus -mediated BRD2 knockdown markedly attenuated inflammatory responses and, reduced lipid accumulation and liver injury in EtOH-fed mice. Mechanistically, BRD2 modulates macrophage activation through the Nuclear Factor Kappa B (NF-κB) signaling pathway, as evidenced by altered P65 phosphorylation following BRD2 manipulation. Furthermore, we identified a paracrine interaction between BRD2-activated macrophages and hepatocytes, wherein inflammatory mediators from BRD2-overexpressing macrophages promoted lipid accumulation in hepatocytes. These findings highlight that BRD2 as a key epigenetic regulator of inflammation and lipid metabolism in ALI, offering a promising therapeutic target for addressing both inflammatory and metabolic components of the disease.