Epitranscriptomic Role of m6A in Obesity-Associated Disorders and Cancer Metabolic Reprogramming

Abstract

The global rise in obesity and its associated metabolic disorders underscores the need for a deeper investigation into their underlying molecular mechanisms. While genetic factors are well-established contributors, recent research has increasingly focused on epigenetic regulators, particularly N6-methyladenosine (m6A)—the most prevalent internal RNA modification in eukaryotes. This post-transcriptional modification plays a crucial role in RNA metabolism by regulating mRNA stability, splicing, nuclear export, and translation efficiency. Notably, emerging evidence implicates m6A in both adipogenesis and metabolic dysregulation. In this review, we systematically examine three key dimensions: (1) the molecular mechanisms of m6A modification, including writers, erasers, and readers, in obesity; (2) dysregulated m6A patterns in obesity-related pathologies, such as type 2 diabetes (T2D), insulin resistance, metabolic dysfunction-associated steatotic liver disease (MASLD), and the glycolysis in cancer cells; and (3) the therapeutic potential of targeting m6A and the regulators. By critically assessing recent advancements, we highlight m6A’s dual role as both a metabolic sensor and a disease modulator, offering novel insights into potential strategies for combating obesity-related metabolic syndromes.