Epitranscriptomic Remodeling: m6A Methylation as a Master Regulator of de novo Lipogenesis in MASLD

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is rapidly being recognized as a world health crisis, touching nearly a third of the world’s population. A key step in the progression of MASLD from simple steatosis to full-blown fibrosis is the unregulated lipid metabolism of the liver, especially the overexpression of de novo lipogenesis (DNL). Researchers have identified RNA methylation in the form of N-6 Methyladenosine (m6A) as the master regulator of this unregulated lipid metabolism. It incorporates different regulators, termed writers, erasers, and readers, which determine the fate of lipid metabolism regulator transcripts. In MASLD, these regulators have been found to be compromised, especially in instances where the regulators expression are altered which results in the stabilization of lipid regulators such as SREBP-1c, FASN etc. However, of specific interest is the fact that m6A regulators are connected not only to lipid synthesis but also integrate signals of insulin resistance, oxidative stress, and mitochondrial dysfunction. This article aims to explore the relationship between m6A remodeling pathways and DNL in MASLD pathogenesis. It also addresses the therapeutic implications including both synthetic and natural products of these regulators towards managing MASLD by means of epitranscriptomic profiling.