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Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity.

Publication ,  Journal Article
Shao, M; Hepler, C; Zhang, Q; Shan, B; Vishvanath, L; Henry, GH; Zhao, S; An, YA; Wu, Y; Strand, DW; Gupta, RK
Published in: Cell Stem Cell
April 1, 2021

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.

Duke Scholars

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Published In

Cell Stem Cell

DOI

EISSN

1875-9777

Publication Date

April 1, 2021

Volume

28

Issue

4

Start / End Page

685 / 701.e7

Location

United States

Related Subject Headings

  • Obesity
  • Mice, Inbred C57BL
  • Mice
  • Diet, High-Fat
  • Developmental Biology
  • Animals
  • Adipose Tissue, White
  • Adipose Tissue
  • Adipogenesis
  • Adipocytes
 

Citation

APA
Chicago
ICMJE
MLA
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Shao, M., Hepler, C., Zhang, Q., Shan, B., Vishvanath, L., Henry, G. H., … Gupta, R. K. (2021). Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity. Cell Stem Cell, 28(4), 685-701.e7. https://doi.org/10.1016/j.stem.2020.12.008
Shao, Mengle, Chelsea Hepler, Qianbin Zhang, Bo Shan, Lavanya Vishvanath, Gervaise H. Henry, Shangang Zhao, et al. “Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity.Cell Stem Cell 28, no. 4 (April 1, 2021): 685-701.e7. https://doi.org/10.1016/j.stem.2020.12.008.
Shao M, Hepler C, Zhang Q, Shan B, Vishvanath L, Henry GH, et al. Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity. Cell Stem Cell. 2021 Apr 1;28(4):685-701.e7.
Shao, Mengle, et al. “Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity.Cell Stem Cell, vol. 28, no. 4, Apr. 2021, pp. 685-701.e7. Pubmed, doi:10.1016/j.stem.2020.12.008.
Shao M, Hepler C, Zhang Q, Shan B, Vishvanath L, Henry GH, Zhao S, An YA, Wu Y, Strand DW, Gupta RK. Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity. Cell Stem Cell. 2021 Apr 1;28(4):685-701.e7.
Journal cover image

Published In

Cell Stem Cell

DOI

EISSN

1875-9777

Publication Date

April 1, 2021

Volume

28

Issue

4

Start / End Page

685 / 701.e7

Location

United States

Related Subject Headings

  • Obesity
  • Mice, Inbred C57BL
  • Mice
  • Diet, High-Fat
  • Developmental Biology
  • Animals
  • Adipose Tissue, White
  • Adipose Tissue
  • Adipogenesis
  • Adipocytes