{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:58:57Z","timestamp":1790891937499,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36\u00a0\u00b1\u00a012 years) and 12\u00a0healthy controls (four women, aged 40\u00a0\u00b1\u00a013 years) were studied. Several molecular markers of lipid transport\/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (<jats:italic>Pygm<\/jats:italic> p.50R*\/p.50R*) and wild\u2010type male mice. Peak oxygen uptake (), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate\u2010associated workload were determined by indirect calorimetry during an incremental cycle\u2010ergometer test. Despite having a much lower  (24.7\u00a0\u00b1\u00a04 <jats:italic>vs<\/jats:italic>. 42.5\u00a0\u00b1\u00a011.4\u00a0mL\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>, respectively; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001), patients showed considerably higher values for the MFO rate (0.53\u00a0\u00b1\u00a00.12 <jats:italic>vs<\/jats:italic>. 0.33\u00a0\u00b1\u00a00.10 g\u00a0min<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.001), and for the FATmax (94.4\u00a0\u00b1\u00a07.2 <jats:italic>vs<\/jats:italic>. 41.3\u00a0\u00b1\u00a09.1 % of , <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and MFO rate\u2010associated workload (1.33\u00a0\u00b1\u00a00.35 <jats:italic>vs<\/jats:italic>. 0.81\u00a0\u00b1\u00a00.54\u00a0W\u00a0kg<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.020) than controls. No between\u2010group differences were found overall in molecular markers of lipid transport\/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near\u2010maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15357-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Physically active McArdle patients show an exceptional fat oxidation capacity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Maximal fat oxidation rate occurs near\u2010maximal exercise capacity in these patients.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>McArdle patients\u2019 exercise tolerance might rely on maximal fat oxidation rate capacity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hyperpnoea might cloud substrate oxidation measurements in some patients.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>An animal model revealed overall no higher molecular markers of lipid transport\/metabolism.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp283743","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T16:24:36Z","timestamp":1668270276000},"page":"551-566","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease"],"prefix":"10.1113","volume":"601","author":[{"given":"Carlos","family":"Rodriguez\u2010Lopez","sequence":"first","affiliation":[{"name":"Department of Geriatrics Hospital General Universitario Gregorio Mara\u00f1\u00f3n. Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM)  Madrid Spain"},{"name":"GENUD Toledo Research Group Universidad de Castilla\u2010La Mancha  Toledo Spain"},{"name":"CIBER of Frailty and Healthy Aging (CIBERFES)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Santalla","sequence":"additional","affiliation":[{"name":"Department of Sport and Computer Science Section of Physical Education and Sports Faculty of Sport Universidad Pablo de Olavide  Seville Spain"},{"name":"EVOPRED Research Group Universidad Europea de Canarias  Tenerife Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro. L","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital \u201812 de Octubre\u2019 (\u2018imas12\u2019)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Real\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Mitochondrial and Neuromuscular Disorders Unit Vall d'Hebron Institut de Recerca Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"CIBER for rare disease (CIBERER)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Villarreal\u2010Salazar","sequence":"additional","affiliation":[{"name":"Mitochondrial and Neuromuscular Disorders Unit Vall d'Hebron Institut de Recerca Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"CIBER for rare disease (CIBERER)  Madrid 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