Regulation of exercise-induced lipid metabolism in skeletal muscle

New Findings What is the topic of this review? This report addresses novel mechanisms regulating the utilization of long-chain fatty acids, with emphasis on FAT/CD36 and lipolysis of intramuscular triacylglycerol in skeletal muscle during exercise and contractions. What advances does it highlight? Recent findings show that adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) collectively account for at least 98% of total triacylglycerol lipase activity in skeletal muscle during muscle contractions. The relative importance of HSL and ATGL for breakdown of intramuscular triacylglycerol during muscle contractions is discussed. Collectively, these findings contribute to the understanding of skeletal muscle lipid metabolism during exercise and muscle contractions. Exercise increases the utilization of lipids in muscle. The sources of lipids are long-chain fatty acids taken up from the plasma and fatty acids released from stores of intramuscular triacylglycerol by the action of intramuscular lipases. In the present review, we focus on the role of fatty acid binding proteins, particularly fatty acid translocase/cluster of differentiation 36 (FAT/CD36), in the exercise- and contraction-induced increase in uptake of long-chain fatty acids in muscle. The FAT/CD36 translocates from intracellular depots to the surface membrane upon initiation of exercise/muscle contractions. This occurs independently of AMP-activated protein kinase, and data suggest that Ca2+-related signalling is responsible. The FAT/CD36 has an important role; long-chain fatty acid uptake is markedly decreased in FAT/CD36 knockout mice during contractions/exercise compared with wild-type control mice. In skeletal muscle, 98% of the lipase activity is accounted for by adipose triglyceride lipase and hormone-sensitive lipase. Give that inhibition or knockout of hormone-sensitive lipase does not impair lipolysis in muscle during contraction, the data point to an important role of adipose triglyceride lipase in regulation of muscle lipolysis. Although the molecular regulation of the lipases in muscle is not understood, it is speculated that intramuscular lipolysis may be regulated in part by the availability of the plasma concentration of long-chain fatty acids.