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.