{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T07:52:57Z","timestamp":1791100377530,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T00:00:00Z","timestamp":1457049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2016,4,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>This study aimed to provide molecular insight into the differential effects of age and physical inactivity on the regulation of substrate metabolism during moderate\u2010intensity exercise.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using the arteriovenous balance technique, we studied the effect of immobilization of one leg for 2\u00a0weeks on leg substrate utilization in young and older men during two\u2010legged dynamic knee\u2010extensor moderate\u2010intensity exercise, as well as changes in key proteins in muscle metabolism before and after exercise.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Age and immobilization did not affect relative carbohydrate and fat utilization during exercise, but the older men had higher uptake of exogenous fatty acids, whereas the young men relied more on endogenous fatty acids during exercise.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using a combined whole\u2010leg and molecular approach, we provide evidence that both age and physical inactivity result in intramuscular lipid accumulation, but this occurs only in part through the same mechanisms.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Age and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2\u00a0weeks of unilateral leg immobilization on substrate utilization across the legs during moderate\u2010intensity exercise in young (<jats:italic>n<\/jats:italic>\u00a0=\u00a017; 23\u00a0\u00b1\u00a01\u00a0years old) and older men (<jats:italic>n<\/jats:italic>\u00a0=\u00a015; 68\u00a0\u00b1\u00a01\u00a0years old), while the contralateral leg served as the control. After immobilization, the participants performed two\u2010legged isolated knee\u2010extensor exercise at 20\u00a0\u00b1\u00a01\u00a0W (\u223c50% maximal work capacity) for 45\u00a0min 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 (respiratory quotient) did not differ between groups or legs. Leg fatty acid uptake was greater in older than in young men, and although young men demonstrated net leg glycerol release during exercise, older men showed net glycerol uptake. At baseline, IMTG, muscle pyruvate dehydrogenase complex activity and the protein content of adipose triglyceride lipase, acetyl\u2010CoA carboxylase 2 and AMP\u2010activated protein kinase (AMPK)\u03b33 were higher in young than in older men. Furthermore, adipose triglyceride lipase, plasma membrane\u2010associated fatty acid binding protein and AMPK\u03b33 subunit protein contents were lower and IMTG was higher in the immobilized than the contralateral leg in young and older men. Thus, immobilization and age did not affect substrate choice (respiratory quotient) during moderate exercise, but the whole\u2010leg and molecular differences in fatty acid mobilization could explain the age\u2010 and immobilization\u2010induced IMTG accumulation.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp271712","type":"journal-article","created":{"date-parts":[[2016,1,23]],"date-time":"2016-01-23T09:10:43Z","timestamp":1453540243000},"page":"2339-2358","source":"Crossref","is-referenced-by-count":23,"title":["The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate\u2010intensity exercise in human skeletal muscle"],"prefix":"10.1113","volume":"594","author":[{"given":"A.","family":"Vigels\u00f8","sequence":"first","affiliation":[{"name":"XLAB, Center for Healthy Aging, Department of Biomedical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Gram","sequence":"additional","affiliation":[{"name":"XLAB, Center for Healthy Aging, Department of Biomedical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Dybboe","sequence":"additional","affiliation":[{"name":"XLAB, Center for Healthy Aging, Department of Biomedical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Section of Molecular Physiology, The August Krogh Centre, Department of Nutrition, Exercise and Sports University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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L.","family":"Greenhaff","sequence":"additional","affiliation":[{"name":"MRC\/Arthritis Research UK Centre for Musculoskeletal Ageing Research, Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, School of Life Sciences, The Medical School University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Constantin\u2010Teodosiu","sequence":"additional","affiliation":[{"name":"MRC\/Arthritis Research UK Centre for Musculoskeletal Ageing Research, Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, School of Life Sciences, The Medical School University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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