Critical roles of FTO-mediated mRNA m6A demethylation in regulating adipogenesis and lipid metabolism: Implications in lipid metabolic disorders

Zhou Yang; Guang-li Yu; Xiao Zhu; Tian-hong Peng; Yun-cheng Lv

doi:10.1016/j.gendis.2021.01.005

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Critical roles of FTO-mediated mRNA m6A demethylation in regulating adipogenesis and lipid metabolism: Implications in lipid metabolic disorders

Review article | 更新时间：2022-06-24

- Critical roles of FTO-mediated mRNA m6A demethylation in regulating adipogenesis and lipid metabolism: Implications in lipid metabolic disorders
- Critical roles of FTO-mediated mRNA m6A demethylation in regulating adipogenesis and lipid metabolism: Implications in lipid metabolic disorders
- Genes & Diseases 2022年9卷第1期
- 作者机构：
  
  1. Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical College, University of South China,Hunan,Hengyang,PR China,421001
  2. Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University,Guangxi,Guilin,PR China,541199
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2021.01.005
  中图分类号：
- 纸质出版日期：2022，
  
  网络出版日期：2022-1-1，
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Zhou Yang, Guang-li Yu, Xiao Zhu, 等. Critical roles of FTO-mediated mRNA m6A demethylation in regulating adipogenesis and lipid metabolism: Implications in lipid metabolic disorders[J]. Genes & Diseases, 2022,9(1).

Zhou Yang, Guang-li Yu, Xiao Zhu, et al. Critical roles of FTO-mediated mRNA m6A demethylation in regulating adipogenesis and lipid metabolism: Implications in lipid metabolic disorders[J]. Genes & Diseases, 2022,9(1).
Zhou Yang, Guang-li Yu, Xiao Zhu, 等. Critical roles of FTO-mediated mRNA m6A demethylation in regulating adipogenesis and lipid metabolism: Implications in lipid metabolic disorders[J]. Genes & Diseases, 2022,9(1). DOI： 10.1016/j.gendis.2021.01.005.

Zhou Yang, Guang-li Yu, Xiao Zhu, et al. Critical roles of FTO-mediated mRNA m6A demethylation in regulating adipogenesis and lipid metabolism: Implications in lipid metabolic disorders[J]. Genes & Diseases, 2022,9(1). DOI： 10.1016/j.gendis.2021.01.005.

摘要

Abstract

The goal this review is to clarify the effects of the fat mass and obesity-associated protein (FTO) in lipid metabolism regulation and related underlying mechanisms through the FTO-mediated demethylation of m

A modification. FTO catalyzes the demethylation of m

A to alter the processing

maturation and translation of the mRNAs of lipid-related genes. FTO overexpression in the liver promotes lipogenesis and lipid droplet (LD) enlargement and suppresses CPT-1–mediated fatty acid oxidation via the SREBP1c pathway

promoting excessive lipid storage and nonalcoholic fatty liver diseases (NAFLD). FTO enhances preadipocyte differentiation through the C/EBPβ pathway

and facilitates adipogenesis and fat deposition by altering the alternative splicing of RUNX1T1

the expression of PPARγ and ANGPTL4

and the phosphorylation of PLIN1

whereas it inhibits lipolysis by inhibiting IRX3 expression and the leptin pathway

causing the occurrence and development of obesity. Suppression of the PPARβ/δ and AMPK pathways by FTO-mediated m

A demethylation damages lipid utilization in skeletal muscles

leading to the occurrence of diabetic hyperlipidemia. m

A demethylation by FTO inhibits macrophage lipid influx by downregulating PPARγ protein expression and accelerates cholesterol efflux by phosphorylating AMPK

thereby impeding foam cell formation and atherosclerosis development. In summary

FTO-mediated m

A demethylation modulates the expression of lipid-related genes to regulate lipid metabolism and lipid disorder diseases.

关键词

Keywords

Adipose tissueFTOLipid disorder diseasesLipid metabolismLiverSkeletal muscle

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