Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity.

Journal Article (Journal Article)

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 with the PDGFR antagonist Imatinib, which promotes adipocyte hyperplasia and glucose tolerance in a progenitor cell PPARγ-dependent manner. Our studies unveil a mechanism underlying depot-specific responses of APCs to high-fat feeding and highlight the potential for APCs to be targeted pharmacologically to improve metabolic health in obesity.

Full Text

Duke Authors

Cited Authors

  • Shao, M; Hepler, C; Zhang, Q; Shan, B; Vishvanath, L; Henry, GH; Zhao, S; An, YA; Wu, Y; Strand, DW; Gupta, RK

Published Date

  • April 1, 2021

Published In

Volume / Issue

  • 28 / 4

Start / End Page

  • 685 - 701.e7

PubMed ID

  • 33539723

Pubmed Central ID

  • PMC8026607

Electronic International Standard Serial Number (EISSN)

  • 1875-9777

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2020.12.008


  • eng

Conference Location

  • United States