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BH3 peptides/mimetics in DTEP buffer (300 mM trehalose, 10 mM HEPES-KOH, 0.1% w/v BSA, 1 mM EDTA, 1 mM EGTA, 80 mM KCl, 5 mM succinate, final pH 7.4) were plated at 70 M l 1 (unless otherwise stated) in triplicate in a black 384-well plate

359 , eaan2788 (2018)

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NNMT is over-expressed in fat and liver tissue in obese, diabetic animals, and genetic knockdown of NNMT protects mice against diet-induced obesity by increasing energy expenditure

In adipocytes, this produces a 1.2 to 1.6-fold increase in intracellular NAD+ Lipogenesis suppression : Increased NAD+ availability in adipocytes suppresses lipogenic pathways, reducing fat synthesis and storage SAM/SAH ratio modulation : Inhibiting NNMT's consumption of SAM alters the SAM/S-adenosylhomocysteine (SAH) ratio, which may affect broader methylation dynamics Muscle effects : In aged mice, NNMT inhibition improved muscle proteome and metabolome profiles through mechanisms distinct from exercise, suggesting direct effects on muscle cell biology How 5-Amino-1MQ Differs from NAD+ Precursors# These approaches are mechanistically complementary, though their combination has not been studied