Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease
| العنوان: | Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease |
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| المؤلفون: | Carlos Rodriguez‐Lopez, Alfredo Santalla, Pedro. L Valenzuela, Alberto Real‐Martínez, Mónica Villarreal‐Salazar, Irene Rodriguez‐Gomez, Tomàs Pinós, Ignacio Ara, Alejandro Lucia |
| المساهمون: | Institut Català de la Salut, [Rodriguez-Lopez C] Department of Geriatrics, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. GENUD Toledo Research Group, Universidad de Castilla-La Mancha, Toledo, Spain. CIBER of Frailty and Healthy Aging (CIBERFES), Madrid, Spain. [Santalla A] Department of Sport and Computer Science, Section of Physical Education and Sports, Faculty of Sport, Universidad Pablo de Olavide, Seville, Spain. EVOPRED Research Group, Universidad Europea de Canarias, Tenerife, Spain. [Valenzuela PL] Instituto de Investigación Sanitaria Hospital ‘12 de Octubre’ (‘imas12’), Madrid, Spain. [Real-Martínez A, Villarreal-Salazar M] Grup de Recerca de Patologia Neuromuscular i Mitocondrial, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBER for rare disease (CIBERER), Madrid, Spain. [Rodriguez-Gomez I] GENUD Toledo Research Group, Universidad de Castilla-La Mancha, Toledo, Spain. CIBER of Frailty and Healthy Aging (CIBERFES), Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::trastornos congénitos del metabolismo de los carbohidratos::enfermedad por almacenamiento de glucógeno::enfermedad por almacenamiento de glucógeno tipo V [ENFERMEDADES], Reacció d'oxidació-reducció, Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Carbohydrate Metabolism, Inborn Errors::Glycogen Storage Disease::Glycogen Storage Disease Type V [DISEASES], Physiology, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Cardiovascular::Heart Function Tests::Exercise Test [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Metabolisme, Errors congènits del, diagnóstico::técnicas y procedimientos diagnósticos::técnicas diagnósticas cardiovasculares::pruebas de función cardíaca::prueba de esfuerzo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Proves d'esforç, metabolismo::metabolismo energético::oxidación-reducción [FENÓMENOS Y PROCESOS], Metabolism::Energy Metabolism::Oxidation-Reduction [PHENOMENA AND PROCESSES] |
| الوصف: | Glycogen store disease; Muscle fatigue; Substrate oxidation Enfermedad de almacenamiento de glucógeno; Fatiga muscular; Oxidación del sustrato Malaltia d'emmagatzematge de glucogen; Fatiga muscular; Oxidació del substrat 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 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R∗/p.50R∗) and wild-type male mice. Peak oxygen uptake (V˙O2peak), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate-associated workload were determined by indirect calorimetry during an incremental cycle-ergometer test. Despite having a much lower V˙O2peak (24.7 ± 4 vs. 42.5 ± 11.4 mL kg−1 min−1, respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min−1, P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of V˙O2peak, P < 0.0001) and MFO rate-associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg−1, P = 0.020) than controls. No between-group 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-maximal 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. Research by the IA and CR-L group is funded by the Biomedical Research Networking Centre on Frailty and Healthy Aging (CIBERFES, CB16/10/00314 and CB16/10/00477). IR-G is supported by a postdoctoral contract from Universidad de Castilla–La Mancha (2021/5937). PLV is supported by a Sara Borrell contract from Instituto de Salud Carlos III (CD21/00138). Research by AL and TP is funded by the Spanish Ministry of Economy and Competitiveness and Fondos FEDER (PI18/00139 and PI19/01313, respectively). |
| وصف الملف: | application/pdf |
| تدمد: | 1469-7793 0022-3751 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2b1c7d1cf6187acc8b5574523ae6f55Test https://doi.org/10.1113/jp283743Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e2b1c7d1cf6187acc8b5574523ae6f55 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14697793 00223751 |
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