Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity.

ABSTRACT: Adipose precursor cells (APCs) exhibit regional variation in response to obesity, for unclear reasons. Here, we reveal that HIFα-induced PDGFRβ signaling within murine white adipose tissue (WAT) PDGFRβ⁺ cells drives inhibitory serine 112 (S112) phosphorylation of PPARγ, the master regulator of adipogenesis. Levels of PPARγ S112 phosphorylation in WAT PDGFRβ⁺ cells are depot dependent, with levels of PPARγ phosphorylation in PDGFRβ⁺ cells inversely correlating with their capacity for adipogenesis upon high-fat-diet feeding. HIFα suppression in PDGFRβ⁺ progenitors promotes subcutaneous and intra-abdominal adipogenesis, healthy WAT remodeling, and improved metabolic health in obesity. These metabolic benefits are mimicked by treatment of obese mice

SUBMITTER: Shao M 

PROVIDER: S-EPMC8026607 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature