m6A demethylase FTO regulate CTNNB1 to promote adipogenesis of chicken preadipocyte

Kan Li; Weichen Huang; Zhijun Wang; Qinghua Nie

doi:10.1186/s40104-022-00795-z

m⁶A demethylase FTO regulate CTNNB1 to promote adipogenesis of chicken preadipocyte

J Anim Sci Biotechnol. 2022 Dec 2;13(1):147. doi: 10.1186/s40104-022-00795-z.

Authors

Kan Li^{1

2}, Weichen Huang^{1

2}, Zhijun Wang^{1

2}, Qinghua Nie^{3

4}

Affiliations

¹ Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, 510642, 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, Guangzhou, 510642, China.
³ Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China. nqinghua@scau.edu.cn.
⁴ 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, Guangzhou, 510642, China. nqinghua@scau.edu.cn.

Abstract

Background: N6-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.

Results: The 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.

Conclusions: m⁶A methylation of RNA was negatively associated with adipogenesis of chicken preadipocytes. FTO could regulate CTNNB1 expression in a demethylation manner to promote lipogenesis.

Keywords: Adipogenesis; CTNNB1; Chicken; FTO; m6A.

Abstract

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