Genetic ablation of CD38 protects against Western diet-induced exercise intolerance and metabolic inflexibility

CD38, a multi-functional membrane receptor and enzyme, consumes NAD+ to generate products such as cyclic-ADP-ribose. CD38 knockout mice show elevated tissue and blood NAD+ level. Chronic feeding of high-fat, high-sucrose diet to wild type mice leads to exercise intolerance and reduced metabolic flexibility. Loss of CD38 by genetic mutation protects mice from diet-induced metabolic deficit. These animal model results suggest that elevation of tissue NAD+ through genetic ablation of CD38 can profoundly alter energy homeostasis in animals that are maintained on a calorically-excessive Western diet. Mouse gastrocnemius muscle samples were used in a factor design, where genotype could be WT or KO, and exercise could be sedentary or treadmill. 4 biological replicates were included in each group.