m6A demethylase FTO regulate CTNNB1 to promote adipogenesis of chicken preadipocyte

Journal of Animal Science and Biotechnology

Research

Kan Li¹  Weichen Huang¹  Qinghua Nie¹  Zhijun Wang¹ 

[1]Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, 510642, Guangzhou, China

[2]National-Local Joint Engineering Research Center for Livestock Breeding, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, 510642, Guangzhou, China

关键词: Adipogenesis;    Chicken;    CTNNB1;    FTO;    mA;   

DOI  :  10.1186/s40104-022-00795-z

 received in 2022-05-17, accepted in 2022-10-11,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundN6-methyladenosine (m6A) is an abundant post-transcriptional RNA modification that affects various biological processes. The fat mass and obesity-associated (FTO) protein, a demethylase encoded by the FTO gene, has been found to regulate adipocyte development in an m6A-dependent manner in multiple species. However, the effects of the m6A methylation and FTO demethylation functions on chicken adipogenesis remain unclear. This study aims to explore the association between m6A modification and chicken adipogenesis and the underlying mechanism by which FTO affects chicken preadipocyte development.ResultsThe association between m6A modification and chicken lipogenesis was assessed by treating chicken preadipocytes with different doses of methyl donor betaine and methylation inhibitor cycloleucine. The results showed that betaine significantly increased methylation levels and inhibited lipogenesis, and the inverse effect was found in preadipocytes after cycloleucine treatment. Overexpression of FTO significantly inhibited m6A levels and promoted proliferation and differentiation of chicken preadipocytes. Silencing FTO showed opposite results. Mechanistically, FTO overexpression increased the expression of catenin beta 1 (CTNNB1) by improving RNA stability in an m6A-dependent manner, and we proved that FTO could directly target CTNNB1. Furthermore, CTNNB1 may be a positive regulator of adipogenesis in chicken preadipocytes.Conclusionsm6A methylation of RNA was negatively associated with adipogenesis of chicken preadipocytes. FTO could regulate CTNNB1 expression in a demethylation manner to promote lipogenesis.

【 授权许可】

CC BY   
© The Author(s) 2022

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