Popescu, R. G.; Dinischiotu, A.; Soare, T.; Vlase, E.; Marinescu, G. C.

Nicotinamide mononucleotide (NMN) has emerged as a promising therapeutic intervention for age-related disorders, including Type 2 Diabetes. In this study, we investigated the effects of NMN treatment on glucose uptake and its underlying mechanisms in various tissue and cell lines. Through a comprehensive proteomic analysis, we uncovered a series of distinct organ-specific effects that contribute to the observed improvements in glucose metabolism. Notably, we observed the upregulation of thermogenic UCP1, promoting enhanced glucose utilization in muscle tissue. Additionally, liver and muscle cells displayed a unique response, characterized by spliceosome down-regulation and concurrent upregulation of chaperones, proteasomes, and ribosomes, leading to a mildly impaired and energy-inefficient protein synthesis machinery. Adipose tissue exhibited increased protein synthesis and degradation, fatty acid degradation, Lysosome and mTOR cell proliferation signalling up-regulation, while showing a surprising repressive effect on mitochondrial biogenesis. Furthermore, our findings revealed a remarkable metabolic rewiring in the brain, involving increased production of ketone bodies, down-regulation of mitochondrial OXPHOS components and the TCA cycle, and the induction of known fasting-associated effects. Collectively, our data elucidate the multifaceted nature of NMN action, highlighting its organ-specific effects and their role in modulating glucose metabolism. These findings deepen our understanding of NMN\'s therapeutic potential and pave the way for novel strategies in managing metabolic disorders.