Fat and carbohydrate metabolism during exercise in late-onset Pompe disease.
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Fat and carbohydrate metabolism during exercise in late-onset Pompe disease. / Preisler, Nicolai; Laforet, Pascal; Madsen, Karen Lindhardt; Hansen, Regitze Sølling; Lukacs, Zoltan; Ørngreen, Mette Cathrine; Lacour, Arnaud; Vissing, John.
in: MOL GENET METAB, Jahrgang 107, Nr. 3, 3, 2012, S. 462-468.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Fat and carbohydrate metabolism during exercise in late-onset Pompe disease.
AU - Preisler, Nicolai
AU - Laforet, Pascal
AU - Madsen, Karen Lindhardt
AU - Hansen, Regitze Sølling
AU - Lukacs, Zoltan
AU - Ørngreen, Mette Cathrine
AU - Lacour, Arnaud
AU - Vissing, John
PY - 2012
Y1 - 2012
N2 - Pompe disease is caused by absence of the lysosomal enzyme acid alpha-glucosidase. It is generally assumed that intra-lysosomal hydrolysis of glycogen does not contribute to skeletal muscle energy production during exercise. However, this hypothesis has never been tested in vivo during exercise. We examined the metabolic response to exercise in patients with late-onset Pompe disease, in order to determine if a defect in energy metabolism may play a role in the pathogenesis of Pompe disease. We studied six adult patients with Pompe disease and 10 healthy subjects. The participants underwent ischemic forearm exercise testing, and peak work capacity was determined. Fat and carbohydrate metabolism during cycle exercise was examined with a combination of indirect calorimetry and stable isotope methodology. Finally, the effects of an IV glucose infusion on heart rate, ratings of perceived exertion, and work capacity during exercise were determined. We found that peak oxidative capacity was reduced in the patients to 17.6 vs. 38.8 ml kg(-1) min(-1) in healthy subjects (p = 0.002). There were no differences in the rate of appearance and rate of oxidation of palmitate, or total fat and carbohydrate oxidation, between the patients and the healthy subjects. None of the subjects improved exercise tolerance by IV glucose infusion. In conclusion, peak oxidative capacity is reduced in Pompe disease. However, skeletal muscle fat and carbohydrate use during exercise was normal. The results indicate that a reduced exercise capacity is caused by muscle weakness and wasting, rather than by an impaired skeletal muscle glycogenolytic capacity. Thus, it appears that acid alpha-glucosidase does not play a significant role in the production of energy in skeletal muscle during exercise.
AB - Pompe disease is caused by absence of the lysosomal enzyme acid alpha-glucosidase. It is generally assumed that intra-lysosomal hydrolysis of glycogen does not contribute to skeletal muscle energy production during exercise. However, this hypothesis has never been tested in vivo during exercise. We examined the metabolic response to exercise in patients with late-onset Pompe disease, in order to determine if a defect in energy metabolism may play a role in the pathogenesis of Pompe disease. We studied six adult patients with Pompe disease and 10 healthy subjects. The participants underwent ischemic forearm exercise testing, and peak work capacity was determined. Fat and carbohydrate metabolism during cycle exercise was examined with a combination of indirect calorimetry and stable isotope methodology. Finally, the effects of an IV glucose infusion on heart rate, ratings of perceived exertion, and work capacity during exercise were determined. We found that peak oxidative capacity was reduced in the patients to 17.6 vs. 38.8 ml kg(-1) min(-1) in healthy subjects (p = 0.002). There were no differences in the rate of appearance and rate of oxidation of palmitate, or total fat and carbohydrate oxidation, between the patients and the healthy subjects. None of the subjects improved exercise tolerance by IV glucose infusion. In conclusion, peak oxidative capacity is reduced in Pompe disease. However, skeletal muscle fat and carbohydrate use during exercise was normal. The results indicate that a reduced exercise capacity is caused by muscle weakness and wasting, rather than by an impaired skeletal muscle glycogenolytic capacity. Thus, it appears that acid alpha-glucosidase does not play a significant role in the production of energy in skeletal muscle during exercise.
KW - Humans
KW - Male
KW - Female
KW - Age of Onset
KW - Case-Control Studies
KW - Infusions, Intravenous
KW - Isotope Labeling
KW - Oxygen Consumption
KW - Exercise
KW - Calorimetry, Indirect
KW - Fatty Acids/metabolism
KW - Glucose/administration & dosage
KW - Glycogen/metabolism
KW - Glycogen Storage Disease Type II/metabolism/pathology
KW - Glycogenolysis
KW - Muscle Weakness/metabolism/pathology
KW - Muscle, Skeletal/metabolism/pathology
KW - Physical Exertion
KW - alpha-Glucosidases/metabolism
KW - Humans
KW - Male
KW - Female
KW - Age of Onset
KW - Case-Control Studies
KW - Infusions, Intravenous
KW - Isotope Labeling
KW - Oxygen Consumption
KW - Exercise
KW - Calorimetry, Indirect
KW - Fatty Acids/metabolism
KW - Glucose/administration & dosage
KW - Glycogen/metabolism
KW - Glycogen Storage Disease Type II/metabolism/pathology
KW - Glycogenolysis
KW - Muscle Weakness/metabolism/pathology
KW - Muscle, Skeletal/metabolism/pathology
KW - Physical Exertion
KW - alpha-Glucosidases/metabolism
M3 - SCORING: Journal article
VL - 107
SP - 462
EP - 468
JO - MOL GENET METAB
JF - MOL GENET METAB
SN - 1096-7192
IS - 3
M1 - 3
ER -