Skeletal muscle trafficking and oxidation of fatty acids: Animal and human models

Skeletal muscle receives two sources of fatty acids from the plasma that supply its lipid pools (triglyceride and phospholipid): (1) non-esterified fatty acids bound to albumin (NEFA) and (2) lipoprotein triglyceride esterified fatty acids (Ptg(fa)). The fate of the plasma fatty acids once they enter the muscle, whether stored in the lipid pools, or oxidized for the production of energy, is not well characterized. To better understand trafficking and oxidation of plasma fatty acids by skeletal muscle, strategies based on stable isotopic tracer methods were developed using an animal model, and then applied to humans undergoing exercise.; Animal model. Examining the incorporation of labeled NEFA into the triglyceride and phospholipid pools of skeletal muscle, in combination with the release of labeled CO₂ as a marker for oxidation, provided a demonstration that the system of storage and oxidation of fatty acids could be deconstructed. Labeled fatty acids could be traced into the circulating Ptg(fa) and also used to determine their contribution to storage. The proportional contribution of fatty acids to fat oxidation was demonstrated for the first time: NEFA, Ptg(fa), and muscle lipid all contributing one-third to the total.; Human model. A gender comparison of skeletal muscle fatty acid trafficking and oxidation was made in endurance-trained athletes cycling at a moderate intensity for two hours. Several differences were observed for fat metabolism between men and women over time: (1) Women had significantly higher whole body fat oxidation than the men, explained predominantly by elevated levels of NEFA oxidation. (2) The total distribution of fatty acids available for fat oxidation by skeletal muscle was opposite in the men and women. The women had a significantly greater breakdown of muscle triglyceride fatty acids in the first half hour of exercise, with accompanying delivery of NEFA and Ptg(fa), while the men had a similar profile in the final half hour of exercise. Finally, it was determined that in active skeletal muscle there was a high level of turnover in the muscle triglyceride pool relative to the phospholipid pool. A large fraction of the NEFA traversed the muscle triglyceride pool prior to oxidation.