A number of studies support NAD + regeneration as a therapeutic strategy to benefit patients with obesity.[27] For examples, natural NAD + precursor activators such as nicotinamide riboside (NR) administered via dietary supplements to high-fat fed mice protected against diet-induced obesity, increased energy metabolism, and improved insulin sensitivity;[41] some of these effects were shown to be mediated by NAD + -dependent SIRT1 activation.[42] Similarly, systemic administration of NMN improved glucose tolerance and diet- and age-related insulin resistant conditions.[43, 44] However, dietary supplemental NAD + precursors (e.g., NR, NMN) require chronic administration and/or very high pharmacological doses to achieve physiologically beneficial enhancements in the NAD + levels, which potentially limit use in humans.[27] It could be predicted that combined administration of sub-maximal doses of dietary supplements and NNMT inhibitors that function as activators of NAD + might produce synergistic improvements in diet-induced obesity, and reduce adverse effects associated with chronic high-dose administration of dietary supplemental NAD + precursors
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