PDGFR{alpha} / PDGFR{beta} signaling balance modulates progenitor cell differentiation into white and beige adipocytes [RESEARCH ARTICLE]

Zhanguo Gao, Alexes C. Daquinag, Fei Su, Brad Snyder, and Mikhail G. Kolonin

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 PDGFRα or PDGFRβ, in adipose tissue function have remained unclear. Here, by defining the developmental timing of PDGFRα and PDGFRβ expression in mouse subcutaneous and visceral adipose depots, we uncover depot-specificity of preadipocyte delineation. We demonstrate that PDGFRα expression precedes PDGFRβ expression in all subcutaneous but only in a fraction of visceral adipose stromal cells. We show that high fat diet feeding or thermoneutrality in early postnatal development can induce PDGFRβ+ lineage recruitment to generate white adipocytes. In contrast, the contribution of PDGFRβ+ 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 PDGFRβ expression. Based on PDGFRα or PDGFRβ deletion and ectopic expression experiments, we conclude that the PDGFRα / PDGFRβ signaling balance determines progenitor commitment to beige or white adipogenesis, respectively. Our study suggests that adipocyte lineage specification and metabolism can be modulated through PDGFR signaling.

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