Figure 2.

Integration of carbohydrate and lipid metabolism in skeletal muscle cells during exercise. Fat and carbohydrate are important fuels for aerobic exercise and there can be reciprocal shifts depending on the exercise intensity and duration. During prolonged exercise at a low to moderate intensity (35% of VO_2max), most of the energy requirements for skeletal muscle can be met from predominantly FA oxidation, with a very small contribution from glucose oxidation. Increases in exercise intensity produce a progressive shift in energy contribution from fat towards carbohydrate, until it reaches 95% of VO_2max, when glucose becomes the main energy source of fuel for skeletal muscle contraction. The figure also shows the regulation involving many sites of control (transport of FFAs into the muscle cell by FA binding protein of the plasma membrane (FABPpm) and FAT/CD36, and into the mitochondria via carnitine palmitoyl transferase (CPT1/CPT2) and the role of carnitine-acylcarnitine translocase (CACT)). When glycolytic flux is increased, as during high-intensity aerobic exercise, the enhanced pyruvate production leads to acetyl-CoA excess and ATP resynthesis at high-energy requirements. At lower exercise intensities or during prolonged exercise, a lower glycolytic rate decreases the supply of glycolysis-derived acetyl-CoA and the reduced sequestration of carnitine enables increased FA import through CPT1 and carnitine shuttle system, favoring utilization of β-oxidation-derived acetyl-CoA in the TCA cycle and ultimately FA oxidation.