In mammalian cells, NAD plays a crucial role in metabolism, DNA repair, epigenetic regulation, senescence, and immunoregulation.[10, 11] Disruption of cellular NAD homeostasis involves in a lot of diseases, such as aging, obesity, diabetes, alcoholic or nonalcoholic liver disease, and also IR‐related organ injury, such as heart, brain, and kidney.[6, 7, 10, 12, 13, 14] For example, it has been demonstrated that over activation of CD38 leads to NAD depletion in cardiac ischemic injury.[15] Genetic or pharmacological blockade of CD38 can notably rescue the outcome. Here, CD38 is linked to obesity due to melanocortin 4 receptor deficiency.