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 tracers125I-labeled β-methyl- p-iodophenylpentadecanoic acid (BMIPP) and deoxy-[2-3H]glucose (DG) during treadmill exercise with and without inhibition of NOS. [125I]BMIPP uptake at rest differed substantially among tissues with the highest levels in heart. With exercise, [125I]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 [125I]BMIPP uptake. In contrast, exercise, but not l-NAME feeding, resulted in increased heart and skeletal muscle [2-3H]DG uptake. Significant interactions were not observed in the effects of combined exercise and l-NAME feeding on [125I]BMIPP and [2-3H]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.