Exploring NNMT: from metabolic pathways to therapeutic targets

Cellular metabolism-related epigenetic modulation plays a pivotal role in the maintenance of cellular homeostasis. Nicotinamide N-methyltransferase (NNMT) serves as a crucial link between cellular metabolism and epigenetics by catalyzing nicotinamide methylation using the universal methyl donor S-adenosyl-L-methionine. This direct connection bridges the methylation-mediated one-carbon metabolism with nicotinamide adenine dinucleotide levels. Numerous studies have revealed tissue-specific differences in NNMT expression and activity, indicating that its varied physiological and pathological roles depend on its distribution. In this review, we provide an overview of the NNMT involvement in various pathological conditions, including cancer, liver disease, obesity, diabetes, brain disease, pulmonary disease, cardiovascular disease, and kidney disease. By synthesizing this information, our article aims to enhance our understanding of the cellular mechanisms underlying NNMT biology related to diverse diseases and lay the molecular groundwork for developing therapeutic strategies for pharmacological interventions.