Johnsson_2025_Am.J.Physiol.Endocrinol.Metab__

Individuals with obesity and endurance exercise-trained athletes both exhibit excess lipid content in their skeletal muscle compared to healthy, sedentary individuals, yet they experience vastly different health outcomes. Lipids taken up from the circulation contribute to lipid stored in muscle in both populations. Differences in the muscle uptake of plasma non-esterified fatty acids (NEFA) and fatty acids derived from plasma triacylglycerol (TG) between individuals with obesity and endurance-trained athletes have not been systematically examined. In athletes, muscle actively regulates the uptake of TG-derived fatty acids through upregulation of the activity of muscle lipoprotein lipase - the enzyme responsible for the intravascular hydrolysis of TG, a phenomenon evident in the fasting state. In contrast, in individuals with obesity, skeletal muscle functions as a passive recipient of TG-derived fatty acids, an event that becomes quantitively more important when the plasma TG concentrations increase during the postprandial state. Considerable differences in the muscle uptake of plasma NEFA between athletes and individuals with obesity are less evident. These observations indicate mechanistic differences in the regulation of plasma TG-derived fatty acids uptake in muscle between individuals with obesity and endurance-trained athletes in shaping the excess lipid content in their muscles. Moreover, this evidence highlights the need for targeting a reduction in plasma TG in the postprandial state when aiming to attenuate lipid accumulation in muscle in the pathophysiology of obesity.