Mitochondrial Substrates Utilization by Skeletal Muscles in Rats after a 5500m Simulated Exposure: 2737

Recent studies have associated exposure to high altitude with a reduced muscle mass, while total mitochondrial volume density or mitochondrial oxidative capacities were affected differently depending on muscle metabolism. Little is known concerning the impact of chronic hypoxia on fuel utilization from mitochondria of slow and fast-twitch skeletal muscles. PURPOSE: to examine the effects of chronic hypoxia on in situ skeletal muscle oxidative capacities and mitochondrial substrate's utilization, rats were exposed 3 weeks to a simulated altitude of 5500 m in an hypobaric chamber and compared with control animals resting in normoxic conditions. METHODS: rats were randomly assigned to one of three experimental groups: hypoxic (H), normoxic (N), and N pair fed (PF) to dissociate the respective effects of hypoxia and anorexia. PF animals received a food supply equivalent to the amount consumed by H rats. Mitochondrial oxidative capacities and utilization of non lipid (G3P) and lipid (octanoate) substrates were measured in permeabilized fibers of a slow-oxidative (soleus, SOL) and fast-glycolytic (white gastrocnemius, WG) muscles. RESULTS: In SOL, maximal respiration rate (Vmax) was not altered in H and PF rats. G3P utilization was low (<20% Vmax), but significantly higher in PF (15% Vmax) than in N and H animals (11%, P < 0.05, and 8% Vmax, P < 0.001, respectively). Octanoate consumption represented 59%, 71% and 59% Vmax in N, PF and H rats, respectively, with an increased utilization only in PF animals (P < 0.001). Then, food restriction stimulates octanoate utilization in oxidative muscle. In WG, Vmax decreased in PF and in H rats in comparison with N animals (−21% and −36%, P < 0.001, respectively). In contrast with SOL, octanoate utilization was low (<25% Vmax), but significantly higher in PF (24% Vmax) than in N and H animals (20%, P < 0.05 and 15% Vmax, P < 0.001, respectively). G3P utilization represented 69%, 75% and 85% Vmax in N, PF and H rats, respectively, with a specific increased utilization in H animals (P < 0.001). Hypoxia leads to a higher utilization of G3P in glycolytic muscle. CONCLUSIONS: The effects of chronic hypoxia on the maximal rate of substrate oxidation seem to be dependent on the type of metabolism initially predominant in skeletal muscles. Indeed, our results suggest that WG is sensitive to anorexia but in a more extend to reduced O2 delivery, while SOL is merely responsive to food restriction. These metabolic differences between SOL and WG could be explained by a reduced mitochondrial population in WG muscle of PF and H groups, as previously observed in other fast-twitch skeletal muscles of rats exposed to hypoxia.