PRJNA715815
Gene expression of adipose tisssue macrophages from Brd4-CKO mice was compared to wild type mice
Macrophage mediated inflammatory response has been implicated in the pathogenesis of obesity and insulin resistance. Brd4 has emerged as a key regulator in the innate immune response. However, the role of Brd4 in obesity associated inflammation and insulin resistance remains uncharacterized. Here, we demonstrated that myeloid lineage specific Brd4 knockout mice were protected from HFD induced obesity with less fat accumulation, higher energy expenditure, and increased lipolysis in adipose tissue. Brd4 CKO mice also displayed reduced local and systemic inflammation with improved insulin sensitivity upon HFD. RNA sequencing of ATMs from HFD fed wide type and Brd4 CKO mice revealed that expression of antilipolytic factor Gdf3 was significantly decreased in ATMs of Brd4 CKO mice. Furthermore, Brd4-mediated expression of Gdf3 acted as a paracrine signal targeting adipocytes to suppress the expression of lipases and the associated lipolysis in cultured cells and mice. By controlling the expression of Gdf3 in ATMs, Brd4 modulates lipid metabolism and diet induced obesity, suggesting that Brd4 could be a potential therapeutic target for obesity and insulin resistance.