The Regulation of Fat Metabolism During Aerobic Exercise

Abstract

Since the lipid profile is altered by physical activity, the study of lipid metabolism is a remarkable element in understanding if and how physical activity affects the health of both professional athletes and sedentary subjects. Although not fully defined, it has become clear that resistance exercise uses fat as an energy source. The fatty acid oxidation rate is the result of the following processes: (a) triglycerides lipolysis, most abundant in fat adipocytes and intramuscular triacylglycerol (IMTG) stores, (b) fatty acid transport from blood plasma to muscle sarcoplasm, (c) availability and hydrolysis rate of intramuscular triglycerides, and (d) transport of fatty acids through the mitochondrial membrane. In this review, we report some studies concerning the relationship between exercise and the aforementioned processes also in light of hormonal controls and molecular regulations within fat and skeletal muscle cells.

Keywords: endurance exercise; high-density lipoprotein (HDL); lipid metabolism; lipoprotein; low-density lipoprotein (LDL); plasma fatty acids.

Figure 1

Fatty acid mobilization and utilization in skeletal muscle during endurance exercise. (a) Epinephrine (as well as norepinephrine) and glucagon stimulate FA release from TG stored in adipocyte lipid droplets, with insulin countering their actions. Epinephrine and glucagon bind their specific receptor in the adipocyte membrane, thus stimulating adenylyl cyclase to produce cyclic AMP (cAMP). cAMP activates the cAMP-dependent protein kinase (PKA), which phosphorylates both HSL and perilipin present on the surface of the lipid droplet. The phosphorylation of perilipin increases ATGL activity, thereby providing more diacylglycerol (DAG) substrates to hormone-sensitive lipase (HSL). Hormone-sensitive lipase then hydrolyzes DAG to a free fatty acid (FFA) and MAG, which is further hydrolyzed by a monoacylglycerol lipase (MGL). FFAs are transported to the plasma membrane bound to adipocyte fatty acid-binding protein (aFABP), leave the adipocyte, and bind serum albumin in the blood. (b) Exercise induces lipoprotein lipase (LPL) on the surface of endothelial cells of skeletal muscle. The increased LPL activity increases TG hydrolysis from TG-rich lipoproteins (such as chylomicrons (CM) and very-low density lipoproteins (VLDL)), thus releasing FFA, glycerol, free cholesterol (FC) and phospholipids (PL). The esterified cholesterol is packaged into the core of HDL particles, increasing plasma HDL-C levels. (c) FFA derived from lipoproteins and adipocyte lipolysis are released from the albumin and enter myocytes via specific fatty acid transporters, such as fatty acid translocase (FAT/CD36), plasma membrane-associated fatty acid binding proteins (FABP_pm) and fatty acid transport proteins (FATP). Long-chain FAs bind directly to FATP closely associated with sarcolemmal acyl-Coenzyme A synthethase (ACS). Alternatively, FAs may first bind to FAT/CD36 and then be delivered either to FATP or to cytosolic fatty acid binding proteins (FABP) and activated into acyl-Coenzyme A (acyl-CoA) by intracellular ACS. Acyl-CoA esters enter the mitochondrion via carnitine palmitoyl transferase 1 (CPT1) and are cleaved in the β-oxidation pathway. The acetyl-Coenzyme A molecules produced are oxidized through the tricarboxylic acid cycle (TCA), and the energy of oxidation is conserved in ATP, which fuels muscle contraction and other energy requiring metabolism in the myocyte. FA released from intramyocellular triacylglycerol store (IMTG) through local HSL activity also contribute to lipid utilization in the myofibers during this exercise type.

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.