Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus.

ABSTRACT: Kdm2a catalyzes H3K36me2 demethylation to play an intriguing epigenetic regulatory role in cell proliferation, differentiation, and apoptosis. Herein we found that myeloid-specific knockout of Kdm2a (LysM-Cre-Kdm2a^f/f, Kdm2a^-/-) promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis. Kdm2a^-/- increased H3K36me2 levels at the Pparg locus along with augmented chromatin accessibility and Stat6 recruitment, which rendered macrophages with preferential M2 polarization. Therefore, the Kdm2a^-/- mice were highly protected from high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed ch

SUBMITTER: Chen L 

PROVIDER: S-EPMC8185071 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature