Protein arginine methyltransferases as metabolic regulators: many roles beyond cancer

Metabolic syndrome (MetS) comprises a cluster of interconnected metabolic abnormalities that collectively elevate the risk of cardiovascular disease and mortality. With its global prevalence escalating, understanding the molecular underpinnings of MetS has become increasingly imperative. Protein arginine methyltransferases (PRMTs), classically studied for their epigenetic functions and oncogenic properties, are now recognized as pivotal regulators of metabolic homeostasis. Emerging research reveals that these enzymes coordinate crucial aspects of cellular metabolism through multiple mechanisms, including methylation of metabolic transcription factors, modulation of nutrient-sensing pathways, and direct regulation of enzymatic activities in glucose and lipid metabolism. This review summarizes current knowledge on the metabolic roles of PRMTs, specifying their roles in the development and function of major metabolic tissues and their associations with various metabolic disorders. We further review how PRMTs influence metabolic processes by modifying key transcriptional networks and signaling cascades through methylation of different substrates. By integrating these insights, we establish PRMTs as central players in metabolic regulation and assess their potential as therapeutic targets for metabolic diseases beyond their established roles in cancer biology, thereby providing a framework for future research and clinical development.