title: The roles of transforming growth factor-β and Smad3 signaling in adipocyte differentiation and obesity.
abstract: We aimed at elucidating the roles of transforming growth factor (TGF)-β and Smad3 signaling in adipocyte differentiation (adipogenesis) and in the pathogenesis of obesity. TGF-β/Smad3 signaling in white adipose tissue (WAT) was determined in genetically obese (ob/ob) mice. The effect of TGF-β on adipogenesis was evaluated in mouse embryonic fibroblasts (MEF) isolated both from WT controls and Smad3 KO mice by Oil red-O staining and gene expression analysis. Phenotypic analyses of high-fat diet (HFD)-induced obesity in Smad3 KO mice compared to WT controls were performed. TGF-β/Smad3 signaling was elevated in WAT from ob/ob mice compared to the controls. TGF-β significantly inhibited adipogenesis in MEF, but the inhibitory effects of TGF-β on adipogenesis were partially abolished in MEF from Smad3 KO mice. TGF-β inhibited adipogenesis independent from the Wnt and β-catenin pathway. Smad3 KO mice were protected against HFD-induced insulin resistance. The size of adipocytes from Smad3 KO mice on the HFD was significantly smaller compared to the controls. In conclusion, the TGF-β/Smad3 signaling pathway plays key roles not only in adipogenesis but also in development of insulin resistance.
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Tsurutani
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Takemoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Irisuna
authors.forename: Masaya
authors.initials: M
authors.lastname: Koshizaka
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Onishi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Morito
authors.initials: M
authors.lastname: Mezawa
authors.forename: Peng
authors.initials: P
authors.lastname: He
authors.forename: Satoshi
authors.initials: S
authors.lastname: Honjo
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Maezawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
mesh_terms: D052438:Adipocytes, White / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism*; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D007328:Insulin; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta