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Effects of NNMT inhibitors on 3T3-L1 cell viability The cytotoxic effects of three membrane-permeable NNMT inhibitors, 5-amino-1MQ, 7-amino-1MQ, and 2,3-diamino-1MQ were evaluated in 3T3-L1 pre-adipocytes
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NAD is a vital coenzyme present in every cell , essential for converting nutrients into energy (ATP) through glycolysis, the Krebs cycle, and mitochondrial oxidative phosphorylation
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These cofactors are critical regulators of cellular energy metabolism, polyamine flux, epigenetic remodeling, and SIRT1 activity in the NAD + salvage pathway.[12, 27, 40] The increased levels of SAM and NAD + we observed in cultured adipocytes following NNMT inhibition are consistent with the upregulation of SAM and NAD + observed in the WAT of DIO mice treated with NNMT ASO, which correlated with increased cellular energy expenditure, reduced adiposity, and protection against diet-induced obesity.[12] In the present study, systemic treatment of DIO mice with a small molecule NNMT inhibitor caused significant loss of body weight and WAT mass, reduction in adipocyte size, and corresponding improvements in the plasma lipid profile (i.e., decreased circulating cholesterol levels)
