The role of m6A methyltransferase METTL3 in metabolism-related diseases: Mechanism and clinical implications

Metabolism-related diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), Atherosclerosis (As)，type 2 diabetes mellitus (T2DM), and diabetic complications, are rising at an alarming rate globally, significantly increasing the risk of life-threatening conditions. Furthermore, these diseases have emerged as a major public health challenge worldwide. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification in eukaryotic messenger RNA molecules, catalyzed by methyltransferase complexes, with methyltransferase-like 3 (METTL3) serving as the sole catalytic subunit due to its unique structural properties. As a critical component of the m6A methylation mechanism, METTL3 profoundly influences metabolism-related diseases through various pathways, including the regulation of adipocyte differentiation, modulation of key metabolic genes, and mediation of inflammatory responses via cytokine secretion. This article reviews recent research findings that elucidate the precise molecular mechanisms underlying METTL3's involvement in these processes and assesses its potential as a therapeutic target, along with the associated challenges.