Fatty Acid Transport Protein CD36 Is Essential For The Training-induced Increase In Fatty Acid Oxidation.

Abstract

Exercise training induces metabolic changes in skeletal muscle, among which is an increase in fatty acid oxidation. Whether CD36, the protein responsible for the majority of fatty acid uptake into muscle tissue, is upregulated in response to exercise training is unclear. We hypothesize that a training-induced increase in muscle CD36 is required to observe the training-induced increase in fatty acid oxidation, as this would permit a greater influx of fatty acids to be oxidized. PURPOSE: To determine the role of CD36 in the training-induced adaptations to fatty acid oxidation. METHODS: CD36 knockout (KO) and wild type (WT) mice were treadmill trained for 6 weeks (0.5 h/day at 17m/min, 5 days/week for 2 weeks, then increasing to 1h/day, 5days/week). After training, soleus and EDL muscles were incubated in vitro, and rates of fatty acid esterification and oxidation (caffeine-stimulated, 3mM) were determined in sedentary and trained WT and CD36-KO mice. Activities of citrate synthase (CS) and b-hydroxyacyl-CoA dehydrogenase (b-HAD) and several fatty acid transporters (Western blotting) were also determined in all mice. RESULTS: The training-induced increase in mitochondrial biogenesis was comparable in WT and CD36-KO mice, as shown by their similar increase in CS activity (p < 0.05). However, b-HAD increased only in WT mice (p < 0.05). Caffeine stimulation increased fatty acid oxidation in muscles of sedentary WT and CD36-KO mice (p < 0.05). However, only the WT mice, not CD36-KO mice, showed an increased response to caffeine-stimulated palmitate oxidation after training (p < 0.05). In addition, CD36 was increased in muscles of WT mice following training (p < 0.05), and there was no detectable CD36 protein in KO mice. Other fatty acid transporters, FABPpm and FATP1 were increased (p < 0.05) in both WT and KO mice. CONCLUSIONS: Although the classical marker of training-induced muscle adaptation (increased CS activity) occurred in both WT and CD36 KO mice, the trained muscles of CD36-KO mice were unable to increase their capacity for fatty acid oxidation. Therefore, CD36 is required for the training-induced increase in fatty acid oxidation in muscle.