We suggest that a depressed and/or metabolically challenged hepatic NAD metabolome is a potential target for NR interventions, and note that people with alcoholic liver disease have depressed hepatic NAD. It is clearly time to perform trials of longer duration, as well as ones that incorporate physical activity, to test the hypothesis that NR supports mobilization of fat from liver and other storage depots in exercised obese adults. If NR does indeed help people mobilize fat, increased physical activity should help people gain lean mass, increase resting metabolic rate, and eventually increase their exercise capacity in lifestyle-modifying ways that promote a virtuous cycle.