Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome

AbstractOxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

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Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity

JCI Insight ◽

10.1172/jci.insight.98081 ◽

2018 ◽

Vol 3 (9) ◽

Cited By ~ 1

Author(s):

Steve Lancel ◽

Matthijs K.C. Hesselink ◽

Estelle Woldt ◽

Yves Rouillé ◽

Emilie Dorchies ◽

...

Keyword(s):

Skeletal Muscle ◽

Energy Metabolism ◽

Endurance Capacity ◽

Muscle Energy ◽

Muscle Energy Metabolism

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Effects of the Anti-Migraine Drug Sumatriptan on Muscle Energy Metabolism: Relationship to Side-Effects

Cephalalgia ◽

10.1046/j.1468-2982.2000.00009.x ◽

2000 ◽

Vol 20 (1) ◽

pp. 39-44 ◽

Cited By ~ 14

Author(s):

MD Boska ◽

KMA Welch ◽

L Schultz ◽

J Nelson

Keyword(s):

Skeletal Muscle ◽

Energy Metabolism ◽

Side Effects ◽

Kinetic Data ◽

Oxygen Storage ◽

Resonance Spectroscopy ◽

Sumatriptan Succinate ◽

Muscle Energy ◽

Creatine Kinase Reaction ◽

Muscle Energy Metabolism

Sumatriptan succinate (Imitrex) is a 5-HT(5-hydroxytryptamine) agonist used for relief of migraine symptoms. Some individuals experience short-lived side-effects, including heaviness of the limbs, chest heaviness and muscle aches and pains. The effects of this drug on skeletal muscle energy metabolism were studied during short submaximal isometric exercises. We studied ATP flux from anaerobic glycolysis (An Gly), the creatine kinase reaction (CK) and oxidative phosphorylation (Ox Phos) using 31P nuclear magnetic resonance spectroscopy (31P MRS) kinetic data collected during exercise. It was found that side-effects induced acutely by injection of 6 mg sumatriptan succinate s.c. were associated with reduced oxygen storage in peripheral skeletal muscle 5–20 min after injection as demonstrated by a transient reduction in mitochondrial function at end-exercise. These results suggest that mild vasoconstriction in peripheral skeletal muscle is associated with the action of sumatriptan and is likely to be the source of the side-effects experienced by some users. Migraine with aura patients were more susceptible to this effect than migraine without aura patients.

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Multinuclear MRS at 7T Uncovers Exercise Driven Differences in Skeletal Muscle Energy Metabolism Between Young and Seniors

Frontiers in Physiology ◽

10.3389/fphys.2020.00644 ◽

2020 ◽

Vol 11 ◽

Author(s):

Patrik Krumpolec ◽

Radka Klepochová ◽

Ivica Just ◽

Marjeta Tušek Jelenc ◽

Ivan Frollo ◽

...

Keyword(s):

Skeletal Muscle ◽

Energy Metabolism ◽

Muscle Energy ◽

Muscle Energy Metabolism

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Regulation of skeletal muscle ATP catabolism by AMPD1 genotype during sprint exercise in asymptomatic subjects

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.1.258 ◽

2001 ◽

Vol 91 (1) ◽

pp. 258-264 ◽

Cited By ~ 46

Author(s):

Barbara Norman ◽

Richard L. Sabina ◽

Eva Jansson

Keyword(s):

Skeletal Muscle ◽

Energy Metabolism ◽

Time Course ◽

Fold Increase ◽

Amp Deaminase ◽

Biopsy Material ◽

Plasma Ammonia ◽

Muscle Energy ◽

Muscle Energy Metabolism ◽

Asymptomatic Subjects

Deficiency of myoadenylate deaminase, the muscle isoform of AMP deaminase encoded by the AMPD1 gene, is a common myopathic condition associated with alterations in skeletal muscle energy metabolism. However, recent studies have demonstrated that most individuals harboring this genetic abnormality are asymptomatic. Therefore, 18 healthy subjects with different AMPD1 genotypes were studied during a 30-s Wingate test in order to evaluate the influence of this inherited defect in AMPD1 expression on skeletal muscle energy metabolism and exercise performance in the asymptomatic population. Exercise performances were similar across the AMPD1 genotypes, whereas significant differences in several descriptors of energy metabolism were observed. Normal homozygotes (NN) exhibited the highest levels of AMP deaminase activities, net ATP catabolism, and IMP accumulation, whereas intermediate values were observed in heterozygotes (MN). Conversely, mutant homozygotes (MM) had very low AMP deaminase activities and showed no significant net catabolism of ATP or IMP accumulation. Accordingly, MM also did not show any postexercise increase in plasma ammonia. Unexpectedly, MN consistently exhibited greater increases in plasma ammonia compared with NN despite the relatively lower accumulation of IMP in skeletal muscle. Moreover, time course profiles of postexercise plasma ammonia and blood lactate accumulation also differed across AMPD1 genotypes. Finally, analysis of adenosine in leftover biopsy material revealed a modest twofold increase in MN and a dramatic 25-fold increase in MM.

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