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In vivo models, typically diet-induced obese (DIO) mice, are needed to assess systemic metabolic effects

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Cytosolic and nuclear NAD + are often considered a shared pool as NAD + diffuses through nuclear pores 58 , and importantly, the concentrations of NAD + in the cytosol, nucleus, and mitochondria mirror the K m of NAD + -consuming enzymes localized to the corresponding compartment, hence these enzymes are sensitive to compartmental fluctuations in NAD + levels 77