m6A甲基化与代谢性疾病调控

N6-methyladenosine methylation and its regulation in metabolic diseases

背景:m6A甲基化修饰已逐渐成为生命科学与运动医学的研究热点与新方向,且诸多研究已证实m6A甲基化修饰与各类疾病关系密切,并在代谢类疾病的诊断和治疗中发挥关键作用,但其机制尚未阐明。目的:探讨m6A甲基化与各类代谢性疾病的关系,综述m6A及相关的酶在代谢性疾病调控中的最新研究进展,并对其具体分子机制进行详细概述,旨在为代谢性疾病的诊疗提供新的方向。方法:以“m6A,obesity,type 2 diabetes,nonalcoholic fatty liver disease,osteoporosis”为英文主题词和“m6A,肥胖,2型糖尿病,非酒精性脂肪肝,骨质疏松”为中文主题词,分别在PubMed和CNKI数据库检索m6A甲基化与各种代谢性疾病发生发展的相关国内外最新研究成果。根据纳入及排除标准最终纳入51篇文献进行归纳总结。结果与结论:①m6A甲基化可通过各种信号通路广泛参与各类代谢性疾病的发生发展,m6A对RNA的动态调控通过相关的酶调节脂肪生成、葡萄糖和脂质代谢、胰岛β细胞功能、胰岛素抵抗、血糖稳态和骨形成等进程,进而在肥胖症、2型糖尿病、非酒精性脂肪肝和骨质疏松症中发挥关键作用。②m6A甲基化酶FTO及相关酶与各类代谢性疾病发生发展关系密切,可作为其诊断的生物标记物。此外,m6A甲基化也可能成为脂肪代谢、脂质分化等进程的有效指标,并为其诊断提供更多的选择。

BACKGROUND:N6-methyladenosine(m6A)methylation has gradually become a research hotspot and new direction in life science and sports medicine.Many studies have confirmed that m6A methylation is closely related to various diseases and plays a key role in the diagnosis and treatment of metabolic diseases,but its mechanism has not been clarified.OBJECTIVE:To investigate the relationship between m6A methylation and various metabolic diseases,to review the latest research progress of m6A and related enzymes in the regulation of metabolic diseases,and to provide a detailed overview of the specific molecular mechanism,in order to provide a new direction for the diagnosis and treatment of metabolic diseases.METHODS:The latest domestic and foreign research results related to m6A methylation and the occurrence and development of various metabolic diseases were searched in PubMed and CNKI with the search terms of“m6A,obesity,type 2 diabetes,nonalcoholic fatty liver disease,osteoporosis”in English and Chinese,respectively.Finally,according to the inclusion and exclusion criteria,51 literatures were finally included and summarized.RESULTS AND CONCLUSION:M6A methylation is widely involved in the occurrence and development of various metabolic diseases through a variety of signaling pathways.The dynamic regulation of m6A on RNA regulates the processes of adipogenesis,glucose and lipid metabolism,isletβcell function,insulin resistance,blood glucose homeostasis and bone formation through related enzymes.In turn,it plays a key role in obesity,type 2 diabetes,nonalcoholic fatty liver disease and osteoporosis.M6A methylase fat mass and obesity-associated protein and related enzymes are closely related to the occurrence and development of various metabolic diseases,and can be used as biomarkers for their diagnosis.In addition,m6A methylation may be an effective indicator of lipid metabolism,lipid differentiation and other processes,and provide more options for relevant diagnosis.