Abstract
During fasting, most tissues including skeletal muscle heavily rely on utilization of fatty acids (FA) and minimize glucose use. In contrast, skeletal muscle prefers carbohydrate use as exercise intensity increases. In mice deficient for CD36 (CD36−/− mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in skeletal muscle even during fasting. In this study, we questioned how exercise endurance is affected during prolonged fasting in CD36−/− mice where glucose utilization is constantly increased. With or without a 24‐h fast, a single bout of treadmill exercise was started at the speed of 10 m/min, and the speed was progressively increased up to 30 m/min until mice were exhausted. Running distance of wild type (WT) and CD36−/− mice was comparable in the fed state whereas that of CD36−/− mice was significantly reduced after a 24‐h fast. Glycogen levels in liver and skeletal muscle were depleted both in WT and CD36−/− mice after a 24‐h fast. In CD36−/− mice, FA uptake by skeletal muscle continued to be reduced during fasting. Glucose utilization also continued to be enhanced in the heart and oxidative skeletal muscle and glucose supply relative to its demand was diminished, resulting in accelerated hypoglycemia. Consequently, available energy substrates from serum and in muscle for exercise performance were very limited in CD36−/− mice during prolonged fasting, which could cause a remarkable reduction in exercise endurance. In conclusion, our study underscores the importance of CD36 for nutrient homeostasis to maintain exercise performance of skeletal muscle when nutrient supply is limited.
Highlights
Exercise and fasting are both in catabolic states, but show distinct fuel selection
We found that fatty acids (FA) uptake by red/oxidative skeletal muscle and blood glucose levels were severely decreased during fasting, which could cause reduced endurance capacity in CD36À/À mice
Effects of fasting on FA and glucose uptake in the heart and skeletal muscles To compare difference of FA and glucose uptake between wild type (WT) and CD36À/À mice in the fed and fasted states, we examined the biodistribution of the slowly oxidized FA analogue 125I-BMIPP and the metabolically trapped glucose analogue 18F-FDG
Summary
Exercise and fasting are both in catabolic states, but show distinct fuel selection. Muscle utilization of circulating NEFA declines modestly, whereas utilization of circulating glucose increases progressively up to near-maximal intensities This coincides with increasing contribution of muscle glycogen to energy provision and absolute rates of carbohydrate oxidation with a majority of energy reliance on muscle glycogen for sustained exercise is different between humans and mice (Pederson et al 2005a,b). We further questioned whether exercise endurance is more severely affected in CD36À/À mice during prolonged fasting, when glycogen storage in liver and skeletal muscle are already depleted prior to exercise. We found that FA uptake by red/oxidative skeletal muscle and blood glucose levels were severely decreased during fasting, which could cause reduced endurance capacity in CD36À/À mice. Our study underscores the importance of CD36 for nutrient homeostasis to maintain exercise performance of skeletal muscle when nutrient supply is limited
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