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

ABSTRACT: 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/?-catenin signal. IGF1 attenuated Wnt/?-catenin signaling by activating Axin2/PPAR? pathways in SVF cells, suggesting IGF1 promotes CD31(-)/34(+)/146(-) bias through tuning Wnt signal. PPAR? response element (PPRE) in Axin2 promoter was crucial for Axin2 upregulation, suggesting that PPAR? transcriptionally activates Axin2. Together, these findings illustrate an Axin2/PPAR? axis in adipogenesis that is particularly attributable to a lineage bias towards CD31(-)/34(+)/146(-) cells, with implications in adipose regeneration.

SUBMITTER: Hu L 

PROVIDER: S-EPMC4509822 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature