M⁶A modification in lipid metabolism and related diseases

This review provides a systematic overview of the specific mechanisms by which N6-methyladenosine (m⁶A) modification regulates lipid synthesis, catabolism, and transport. In addition, we discuss the potential therapeutic significance of m⁶A modification in lipid metabolism-related diseases. Although considerable progress has been made, the mechanisms by which m⁶A modification regulates lipid metabolism remain incompletely understood. Notably, m⁶A regulators such as METTL3 exhibit context-dependent and sometimes opposing effects on lipid accumulation and oxidation. FTO gene variants are significantly associated with an increased risk of obesity; however, the development of FTO inhibitors as therapeutic targets for obesity and lipid metabolism disorders still faces considerable challenges. In non-alcoholic fatty liver disease (NAFLD), m⁶A modification not only contributes to disease development but also participates in its progression. METTL3 and METTL14 also play important roles in the development of atherosclerosis (AS). Collectively, the important role of m⁶A regulatory mechanisms in lipid metabolism and related diseases highlights the potential of targeting m⁶A regulators as a promising therapeutic strategy.