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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)

5-amino-1MQ, an analogue from our initial series of NNMT inhibitors with low IC 50 value (IC 50 = ~1 M;[17]), and high cell membrane permeability (Table 2), produced the greatest reduction of intracellular 1-MNA levels at a concentration of 10 M among tested inhibitors (Figure 2D)

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Glutathione is often called the "master antioxidant" because it is found in nearly every cell in the human body

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