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.

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Chiang SH, Harrington WW, Luo G, Milliken NO, Ulrich JC, Chen J, Rajpal DK, Qian Y, Carpenter T, Murray R, Geske RS, Stimpson SA, Kramer HF, Haffner CD, Becherer JD, Preugschat F, Billin AN