PDGFRα/PDGFRβ signaling balance modulates progenitor cell differentiation into white and beige adipocytes

The relative abundance of thermogenic beige adipocytes and lipid-storing white adipocytes in adipose tissue underlie its metabolic activity. The roles of adipocyte progenitor cells, which express PDGFR alpha or PDGFR beta, in adipose tissue function have remained unclear. Here, by defining the developmental timing of PDGFR alpha and PDGFR beta expression in mouse subcutaneous and visceral adipose depots, we uncover depot specificity of pre-adipocyte delineation. We demonstrate that PDGFR alpha expression precedes PDGFR beta expression in all subcutaneous but in only a fraction of visceral adipose stromal cells. We show that high-fat diet feeding or thermoneutrality in early postnatal development can induce PDGFR beta(+) lineage recruitment to generate white adipocytes. In contrast, the contribution of PDGFR beta(+) lineage to beige adipocytes is minimal. We provide evidence that human adipose tissue also contains distinct progenitor populations differentiating into beige or white adipocytes, depending on PDGFR beta expression. Based on PDGFR alpha or PDGFR beta deletion and ectopic expression experiments, we conclude that the PDGFR alpha/PDGFR beta signaling balance determines progenitor commitment to beige (PDGFR alpha) or white (PDGFR beta) adipogenesis. Our study suggests that adipocyte lineage specification and metabolism can be modulated through PDGFR signaling.