The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate intensity exercise in human skeletal muscle

Age and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2 weeks' unilateral leg immobilization on substrate utilization across the legs during moderate intensity exercise in young (n = 17; 23 ± 1 years) and older (n = 15; 68 ± 1 years) men, while the contralateral leg served as control. After immobilization, the participants performed two-legged isolated knee-extensor exercise at 20 ± 1 Watt (∼50% Wattmax ) for 45 min with catheters inserted in the brachial artery and both femoral veins. Biopsy samples obtained from vastus lateralis muscles of both legs before and after exercise were used for analysis of substrates, protein content and enzyme activities. During exercise, leg substrate utilization (RQ) did not differ between groups or legs. Leg fatty acid (FA) uptake was greater in older than in young men, and while young men demonstrated net leg glycerol release during exercise, older men showed net glycerol uptake. At baseline, IMTG, muscle pyruvate dehydrogenase complex activity, protein content of adipose triglyceride lipase (ATGL), acetyl-CoA carboxylase 2, AMP-activated protein kinase (AMPK)γ3 were higher in young than in older men. Furthermore, ATGL, plasma membrane-associated FA binding protein, and AMPKγ3 subunit protein content were lower and IMTG being higher in the immobilized than the contralateral leg in young and older men. Thus, immobilization and age did not affect substrate choice (RQ) during moderate exercise, but the whole-leg and molecular differences in FA mobilization could explain the age and immobilization induced IMTG accumulation. This article is protected by copyright. All rights reserved.