Contrasting effects of exercise and NOS inhibition on tissue-specific fatty acid and glucose uptake in mice

Isotopic techniques were used to test the hypothesis that exercise and nitric oxide synthase (NOS) inhibition have distinct effects on tissue-specific fatty acid and glucose uptakes in a conscious, chronically catheterized mouse model. Uptakes were measured using the radioactive tracers I-125-labeled beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) and deoxy-[2-H-3]glucose (DG) during treadmill exercise with and without inhibition of NOS. [I-125] BMIPP uptake at rest differed substantially among tissues with the highest levels in heart. With exercise, [I-125] BMIPP uptake increased in both heart and skeletal muscles. In sedentary mice, NOS inhibition induced by nitro-L-arginine methyl ester (L-NAME) feeding increased heart and soleus [I-125] BMIPP uptake. In contrast, exercise, but not L-NAME feeding, resulted in increased heart and skeletal muscle [2-H-3] DG uptake. Significant interactions were not observed in the effects of combined exercise and L-NAME feeding on [I-125] BMIPP and [2-H-3] DG uptakes. In the conscious mouse, exercise and NOS inhibition produce distinct patterns of tissue-specific fatty acid and glucose uptake; NOS is not required for important components of exercise-associated metabolic signaling, or other mechanisms compensate for the absence of this regulatory mechanism.