title: SIRT1 inhibits adipogenesis and promotes myogenic differentiation in C3H10T1/2 pluripotent cells by regulating Wnt signaling.
abstract: BACKGROUND
  The directed differentiation of mesenchymal stem cells (MSCs) is tightly controlled by a complex network. Wnt signaling pathways have an important function in controlling the fate of MSCs. However, the mechanism through which Wnt/β-catenin signaling is regulated in differentiation of MSCs remains unknown. SIRT1 plays an important role in the regulation of MSCs differentiation.
  
  
  RESULTS
  This study aimed to determine the effect of sirtuin 1 (SIRT1) on adipogenesis and myogenic differentiation of C3H10T1/2 cells. First, the MSC commitment and differentiation model was established by using 5-azacytidine. Using the established model, C3H10T1/2 cells were treated with SIRT1 activator/inhibitor during differentiation. The results showed that resveratrol inhibits adipogenic differentiation and improves myogenic differentiation, whereas nicotinamide promotes adipogenic differentiation. Notably, during commitment, resveratrol blocked adipocyte formation and promoted myotubes differentiation, whereas nicotinamide enhanced adipogenic potential of C3H10T1/2 cells. Furthermore, resveratrol elevated the expression of Cyclin D1 and β-catenin in the early stages. The luciferase assay showed that knockdown SIRT1 inhibits Wnt/β-catenin signaling, while resveratrol treatment or overexpression SIRT1 activates Wnt/β-catenin signaling. SIRT1 suppressed the expression of Wnt signaling antagonists sFRP2 and DACT1. Knockdown SIRT1 promoted adipogenic potential of C3H10T1/2 cells, whereas overexpression SIRT1 inhibited adipogenic differentiation and promoted myogenic differentiation.
  
  
  CONCLUSIONS
  Together, our results suggested that SIRT1 inhibits adipogenesis and stimulates myogenic differentiation by activating Wnt signaling.
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 People's Republic of China ; State Key Laboratory of Agricultural Microbiology, Division of Animal Infectious Disease, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070 People's Republic of China ; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070 People's Republic of China.
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 People's Republic of China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 People's Republic of China ; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070 People's Republic of China.
authors.forename: Hongkui
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 People's Republic of China ; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070 People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Peng
authors.affiliation: The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070 People's Republic of China ; Key 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, 430070 People's Republic of China.
authors.forename: Siwen
authors.initials: S
authors.lastname: Jiang
keywords: Adipogenesis; MSCs; Myogenic differentiation; SIRT1; Wnt signaling