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N⁶-腺苷酸甲基化修饰在脂质代谢紊乱疾病中调控作用研究进展

陈书雅, 倪安煜, 钱秋慧, 闫瑾, 王学东, 王慧利^*

苏州科技大学环境科学与工程学院，苏州 215009

摘要

脂质代谢是一个复杂的生理过程，与营养调节、激素平衡和内分泌作用密切相关，它涉及多种因子和信号转导通路的互作。脂质代谢紊乱是诱发多种疾病的主要机制之一，如肥胖症、糖尿病、非酒精性脂肪肝病、肝炎、肝细胞癌及其并发症等。目前越来越多的研究发现RNA上发生的N⁶-腺苷酸甲基化(N⁶-adenylate methylation, m⁶A)“动态修饰”代表了一种全新的“转录后”调控方式，mRNA、tRNA、ncRNA等均可发生m⁶A修饰，m6A修饰异常调控基因表达变化和可变剪切事件发生。据最新文献报道，m⁶A RNA修饰参与了脂质代谢紊乱的表观遗传学调控。本文基于脂质代谢紊乱诱发的主要疾病，综述m⁶A修饰在其发生和发展中的调控作用。这些发现从表观遗传学的角度为进一步深入研究脂质代谢紊乱发病的潜在分子机制提供了依据，为相关疾病的卫生预防、分子诊断和治疗提供参考。

关键词： 脂质代谢紊乱; 肥胖症; 2型糖尿病; 非酒精性脂肪肝; 肝细胞癌症; m6A RNA修饰; 表观遗传

Research progress on regulation of N⁶-adenylate methylation modification in lipid metabolism disorders

CHEN Shu-Ya, NI An-Yu, QIAN Qiu-Hui, YAN Jin, WANG Xue-Dong, WANG Hui-Li^*

School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China

Abstract

Lipid metabolism is a complex physiological process, which is closely related to nutrient regulation, hormone balance and endocrine function. It involves the interactions of multiple factors and signal transduction pathways. Lipid metabolism disorder is one of the main mechanisms to induce a variety of diseases, such as obesity, diabetes, non-alcoholic fatty liver disease, hepatitis, hepatocellular carcinoma and their complications. At present, more and more studies have found that the “dynamic modification” of N6-adenylate methylation (m⁶A) on RNA represents a new “post-transcriptional” regulation mode. m⁶A methylation modification can occur in mRNA, tRNA, ncRNA, etc. Its abnormal modification can regulate gene expression changes and alternative splicing events. Many latest references have reported that m⁶A RNA modification is involved in the epigenetic regulation of lipid metabolism disorder. Based on the major diseases induced by lipid metabolism disorders, we reviewed the regulatory roles of m⁶A modification in the occurrence and development of those diseases. These overall findings inform further in-depth investigations of the underlying molecular mechanisms regarding the pathogenesis of lipid metabolism disorders from the perspective of epigenetics, and provide reference for health prevention, molecular diagnosis and treatment of related diseases.

Key words: lipid metabolism disorder; obesity; type 2 diabetes; non-alcoholic fatty liver disease; hepatocellular carcinoma; m6A RNA modification; epigenetic inheritance

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通讯作者：王慧利　　E-mail: whuili@163.com

引用本文：

陈书雅, 倪安煜, 钱秋慧, 闫瑾, 王学东, 王慧利. N⁶-腺苷酸甲基化修饰在脂质代谢紊乱疾病中调控作用研究进展[J]. 生理学报 2023; 75 (3): 439-450.

CHEN Shu-Ya, NI An-Yu, QIAN Qiu-Hui, YAN Jin, WANG Xue-Dong, WANG Hui-Li. Research progress on regulation of N⁶-adenylate methylation modification in lipid metabolism disorders. Acta Physiol Sin 2023; 75 (3): 439-450 (in Chinese with English abstract).