Oncotarget

Research Papers:

SIRT1 suppresses adipogenesis by activating Wnt/β-catenin signaling in vivo and in vitro

Yuanfei Zhou, Tongxing Song, Jie Peng, Zheng Zhou, Hongkui Wei, Rui Zhou, Siwen Jiang and Jian Peng _

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Oncotarget. 2016; 7:77707-77720. https://doi.org/10.18632/oncotarget.12774

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Abstract

Yuanfei Zhou1,2, Tongxing Song2, Jie Peng2, Zheng Zhou2, Hongkui Wei2, Rui Zhou1,4, Siwen Jiang3,4, Jian Peng2,4

1State Key Laboratory of Agricultural Microbiology, Division of Animal Infectious Disease, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, P. R. China

2Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, P. R. China

3Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry, and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, P. R. China

4The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, P. R. China

Correspondence to:

Jian Peng, email: [email protected]

Keywords: mesenchymal stem cells, adipogenesis, SIRT1, Wnt signaling antagonists, β-catenin

Received: June 13, 2016    Accepted: October 12, 2016    Published: October 20, 2016

ABSTRACT

Sirtuin 1 (SIRT1) regulates adipocyte and osteoblast differentiation. However, the underlying mechanism should be investigated. This study revealed that SIRT1 acts as a crucial repressor of adipogenesis. RNA-interference-mediated SIRT1 knockdown or genetic ablation enhances adipogenic potential, whereas SIRT1 overexpression inhibits adipogenesis in mesenchymal stem cells (MSCs). SIRT1 also deacetylates the histones of sFRP1, sFRP2, and Dact1 promoters; inhibits the mRNA expression of sFRP1, sFRP2, and Dact1; activates Wnt signaling pathways; and suppresses adipogenesis. SIRT1 deacetylates β-catenin to promote its accumulation in the nucleus and thus induces the transcription of genes that block MSC adipogenesis. In mice, the partial absence of SIRT1 promotes the formation of white adipose tissues without affecting the development of the body of mice. Our study described the regulatory role of SIRT1 in Wnt signaling and proposed a regulatory mechanism of adipogenesis.


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