Ahnak stimulates BMP2-mediated adipocyte differentiation through Smad1 activation
- 등재 SCIE, SCOPUS
- 발행기관 Blackwell Publishing Inc.
- 발행년도 2016
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000123088
- 본문언어 영어
- Published As http://dx.doi.org/10.1002/oby.21367
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Objective: Previous reports have indicated that Ahnak-deficient mice were protected from high-fat diet-induced obesity. However, the molecular mechanism in which Ahnak mediates adipocyte differentiation and high-fat diet-induced obesity is unclear. Methods: Adipocytes from Ahnak knockout (Ahnak-/-) mice and knockdown of Ahnak in C3H10T1/2 were used to investigate the function of Ahnak in adipocyte differentiation. Ahnak-induced adipocyte differentiation was analyzed by Oil Red O staining. Results: Adipocytes from Ahnak-/- mice were smaller than those from wild-type mice. Silencing of Ahnak in C3H10T1/2 and adipose tissue-derived mesenchymal stem cells (ADSCs) from Ahnak-/- mice showed severely impaired adipocyte differentiation. Down-regulation of Ahnak in C3H10T1/2 cells and ADSCs from Ahnak-/- mice attenuated the phosphorylation and nuclear localization of Smad1 in response to BMP2, whereas Ahnak overexpression in 3T3-L1 cells significantly increased Smad1 activation. Because PPARγ is a well-known transcriptional factor in adipocyte differentiation, the PPARγ expression in Ahnak-mediated adipocyte differentiation was investigated. Transfection of C3H10T1/2 cells with Ahnak siRNA resulted in reduced PPARγ expression apparently through inhibited binding of Smad1 to the Smad1-binding site in the PPARγ promoter. These results suggest that Ahnak regulates adipogenesis by regulating Smad1-dependent PPARγ expression. Conclusions: A molecular mechanism was proposed in which Ahnak regulates adipocyte differentiation through Smad1 activation. © 2016 The Obesity Society.
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