High intensity exercise inhibits carnitine palmitoyltransferase-I sensitivity to L-carnitine

The decline in fat oxidation at higher power outputs of exercise is a complex interaction between several mechanisms; however, the influence of mitochondrial bioenergetics in this process remains elusive. Therefore, using permeabilized muscle fibers from mouse skeletal muscle, we aimed to determine if acute exercise altered mitochondrial sensitivity to (1) adenosine diphosphate (ADP) and inorganic phosphate (Pi), or (2) carnitine palmitoyltransferase-I (CPT-1) independent (palmitoylcamitine, PC) and dependent [palmitoyl-CoA (P-CoA), malonyl-CoA (M-CoA), and L-carnitine] substrates, in an intensity-dependent manner. As the apparent ADP K-m increased to a similar extent following low (LI) and high (HI) intensity exercise compared with sedentary (SED) animals, and Pi sensitivity was unaltered by exercise, regulation of phosphate provision likely does not contribute to the well-established intensity-dependent shift in substrate utilization. Mitochondrial sensitivity to PC and P-CoA was not influenced by exercise, while M-CoA sensitivity was attenuated similarly following LI and HI. In contrast, CPT-I sensitivity to L-camitine was only altered following HI, as HI exercise attenuated L-camitine sensitivity by similar to 40%. Moreover, modeling the in vivo concentrations of L-camitine and P-CoA during exercise suggests that CPT-I flux is similar to 25% lower following HI, attributed equally to reductions in L-carnitine content and L-carnitine sensitivity. Altogether, these data further implicate CPT-I flux as a key event influencing metabolic interactions during exercise, as a decline in L-carnitine sensitivity in addition to availability at higher power outputs could impair mitochondrial fatty acid oxidation.