IGF1 Promotes Adipogenesis by a Lineage Bias of Endogenous Adipose Stem/Progenitor Cells

Adipogenesis is essential for soft tissue reconstruction following trauma or tumor resection. We demonstrate that CD31−/34+/146− cells, a subpopulation of the stromal vascular fraction (SVF) of human adipose tissue, were robustly adipogenic. Insulin growth factor-1 (IGF1) promoted a lineage bias towards CD31−/34+/146− cells at the expense of CD31−/34+/146+ cells. IGF1 was microencapsulated in poly(lactic-co-glycolic acid) scaffolds and implanted in the inguinal fat pad of C57Bl6 mice. Control-released IGF1 induced remarkable adipogenesis in vivo by recruiting endogenous cells. In comparison with the CD31−/34+/146+ cells, CD31−/34+/146− cells had a weaker Wnt/β-catenin signal. IGF1 attenuated Wnt/β-catenin signaling by activating Axin2/PPARγ pathways in SVF cells, suggesting IGF1 promotes CD31−/34+/146− bias through tuning Wnt signal. PPARγ response element (PPRE) in Axin2 promoter was crucial for Axin2 upregulation, suggesting that PPARγ transcriptionally activates Axin2. Together, these findings illustrate an Axin2/PPARγ axis in adipogenesis that is particularly attributable to a lineage bias towards CD31−/34+/146− cells, with implications in adipose regeneration. Stem Cells 2015;33:2483–2495