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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)

Vidal-Alaball J, Butler CC, Cannings-John R, Goringe A, Hood K, McCaddon A, McDowell I, Papaioannou A