| First Author | Shao M | Year | 2021 |
| Journal | Cell Stem Cell | Volume | 28 |
| Issue | 4 | Pages | 685-701.e7 |
| PubMed ID | 33539723 | Mgi Jnum | J:306569 |
| Mgi Id | MGI:6716378 | Doi | 10.1016/j.stem.2020.12.008 |
| Citation | Shao M, et al. (2021) Pathologic HIF1alpha signaling drives adipose progenitor dysfunction in obesity. Cell Stem Cell 28(4):685-701.e7 |
| abstractText | Adipose precursor cells (APCs) exhibit regional variation in response to obesity, for unclear reasons. Here, we reveal that HIFalpha-induced PDGFRbeta signaling within murine white adipose tissue (WAT) PDGFRbeta(+) cells drives inhibitory serine 112 (S112) phosphorylation of PPARgamma, the master regulator of adipogenesis. Levels of PPARgamma S112 phosphorylation in WAT PDGFRbeta(+) cells are depot dependent, with levels of PPARgamma phosphorylation in PDGFRbeta(+) cells inversely correlating with their capacity for adipogenesis upon high-fat-diet feeding. HIFalpha suppression in PDGFRbeta(+) 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 PPARgamma-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. |
