Cell Metabolism
Volume 23, Issue 2, 9 February 2016, Pages 350-359
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Short Article
Pdgfrβ+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice

https://doi.org/10.1016/j.cmet.2015.10.018Get rights and content
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Highlights

  • Zfp423 expression identifies Pdgfrβ+ perivascular (mural) preadipocytes in adult WAT

  • The abundance of Zfp423+ mural cells increases in hyperplastic WAT depots in obesity

  • Pdgfrβ+ mural cells contribute to white adipocyte hyperplasia in diet-induced obesity

  • Pdgfrβ+ cells contribute to beige adipogenesis only after prolonged cold exposure

Summary

The expansion of white adipose tissue (WAT) in obesity involves de novo differentiation of new adipocytes; however, the cellular origin of these cells remains unclear. Here, we utilize Zfp423GFP reporter mice to characterize adipose mural (Pdgfrβ+) cells with varying levels of the preadipocyte commitment factor Zfp423. We find that adipose tissue contains distinct mural populations, with levels of Zfp423 distinguishing adipogenic from inflammatory-like mural cells. Using our “MuralChaser” lineage tracking system, we uncover adipose perivascular cells as developmental precursors of adipocytes formed in obesity, with adipogenesis and precursor abundance regulated in a depot-dependent manner. Interestingly, Pdgfrβ+ cells do not significantly contribute to the initial cold-induced recruitment of beige adipocytes in WAT; it is only after prolonged cold exposure that these cells differentiate into beige adipocytes. These results provide genetic evidence for a mural cell origin of white adipocytes in obesity and suggest that beige adipogenesis may originate from multiple sources.

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