Abstract 14137: Cd36 Plays a Crucial Role in Exercise Endurance During Prolonged Fasting in Mice
During prolonged fasting, most tissues including the heart and skeletal muscle heavily rely on utilization of fatty acids (FA) released from adipose tissue, while glucose utilization is minimized. CD36 plays an important role in membrane transport of long chain fatty acid (FA) in the heart, skeletal muscle and adipose tissue. Previous studies showed that CD36 knockout (CD36KO) mice have reduced uptake of FA with a remarkable increase in glucose utilization in the heart and skeletal muscle, and lower levels of blood glucose during fasting. Here we show that CD36KO mice exhibit reduced endurance for exercise during prolong fasting. Running exercise was started at the speed of 10 meter/min for 5 min, and the speed was increased at a rate of 5 meter/5 min until mice were exhausted. Running distance of wild type (WT) and CD36KO mice was comparable in the fed state whereas that of CD36KO mice was significantly reduced after overnight fasting. Serum glucose levels were significantly reduced in CD36KO mice compared to WT during fasting, which was more enhanced in both mice by running exercise. Uptake of FA analogue 125I-BMIPP was reduced in both glycolytic and oxidative muscles in CD36KO mice whereas uptake of glucose analogue 18F-FDG was enhanced only in the fasted state in oxidative muscle, suggesting that compensatory uptake of glucose in skeletal muscle in CD36KO mice occurs only when energy supply and storage are very limited. Consistent with this, glycogen levels in quadriceps femoris muscle (consisting of more glycolytic muscle than oxidative) were significantly reduced in CD36KO mice, indicating more glycogen consumption than glucose uptake during fasting. Pyruvate challenge test revealed that gluconeogenesis in liver is also decreased in CD36KO mice. Levels of non-esterified FA and ketone body were comparable between WT and CD36KO mice. Given that carbohydrates and lipids are crucial energy substrates for skeletal muscles, our data suggest that depletion of energy storage in skeletal muscles and diminished supply of energy substrates to the tissues during fasting can cause reduced endurance for exercise in CD36KO mice. Our study underscores the importance of CD36 for nutrient homeostasis to maintain function of skeletal muscle when nutrient supply is limited.
Author Disclosures: H. Haruyama: None. T. Iso: None. H. Sunaga: None. Y. Umbarawan: None. M. Syamsunarno: None. M. Putri: None. H. Matsui: None. T. Yokoyama: None. M. Kurabayashi: None.
- © 2016 by American Heart Association, Inc.