title: 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/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.
authors.affiliation: Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.|Center for Craniofacial Regeneration (CCR), New York, New York, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Hu
authors.affiliation: Center for Craniofacial Regeneration (CCR), New York, New York, USA.
authors.forename: Guodong
authors.initials: G
authors.lastname: Yang
authors.affiliation: Center for Craniofacial Regeneration (CCR), New York, New York, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hägg
authors.affiliation: Center for Craniofacial Regeneration (CCR), New York, New York, USA.
authors.forename: Guoming
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology, New York, New York, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Ahn
authors.affiliation: Center for Craniofacial Regeneration (CCR), New York, New York, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Center for Craniofacial Regeneration (CCR), New York, New York, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Ricupero
authors.affiliation: Department of Plastic Surgery, Columbia University Medical Center, New York, New York, USA.
authors.forename: June
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Plastic Surgery, Columbia University Medical Center, New York, New York, USA.
authors.forename: Christine Hsu
authors.initials: CH
authors.lastname: Rodhe
authors.affiliation: Department of Plastic Surgery, Columbia University Medical Center, New York, New York, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Ascherman
authors.affiliation: Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.affiliation: Center for Craniofacial Regeneration (CCR), New York, New York, USA.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Mao
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D000328:Adult; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I
keywords: Adipose; Axin2; CD146; Insulin growth factor-1; Mesenchymal; PPARγ; Stem cells; Stromal vascular fraction