Exercise training increases mitochondrial content and ex vivo mitochondrial function similarly in patients with type 2 diabetes and in control individuals

Phielix, Esther; Meex, Ruth C. R.; Moonen‐Kornips, Esther; Hesselink, Martine; Schrauwen, Patrick

doi:10.1007/s00125-010-1764-2

Cited by 178 publications

(164 citation statements)

References 22 publications

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“…(17). In any case, the data obtained in the present study are similar to those obtained after substantially following the same protocol of the present study in the healthy control subjects of recent studies (9,23,30). In the present study, after adding cytochrome c to the measuring chamber, the increase in mitochondrial respiration was very small (ϳ2%).…”

Section: Methodological Considerationssupporting

confidence: 91%

Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Salvadego

Domenis

Lazzer

et al. 2013

Journal of Applied Physiology

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Oxidative function during exercise was evaluated in 11 young athletes with marked skeletal muscle hypertrophy induced by long-term resistance training (RTA; body mass 102.6 Ϯ 7.3 kg, mean Ϯ SD) and 11 controls (CTRL; body mass 77.8 Ϯ 6.0 kg). Pulmonary O2 uptake (V O2) and vastus lateralis muscle fractional O2 extraction (by near-infrared spectroscopy) were determined during an incremental cycle ergometer (CE) and one-leg knee-extension (KE) exercise. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers obtained by biopsy. Quadriceps femoris muscle cross-sectional area, volume (determined by magnetic resonance imaging), and strength were greater in RTA vs. CTRL (by ϳ40%, ϳ33%, and ϳ20%, respectively). V O2peak during CE was higher in RTA vs. CTRL (4.05 Ϯ 0.64 vs. 3.56 Ϯ 0.30 l/min); no difference between groups was observed during KE. The O2 cost of CE exercise was not different between groups. When divided per muscle mass (for CE) or quadriceps muscle mass (for KE), V O2 peak was lower (by 15-20%) in RTA vs. CTRL. Vastus lateralis fractional O2 extraction was lower in RTA vs. CTRL at all work rates, during both CE and KE. RTA had higher ADP-stimulated mitochondrial respiration (56.7 Ϯ 23.7 pmol O2·s Ϫ1 ·mg Ϫ1 ww) vs. CTRL (35.7 Ϯ 10.2 pmol O2·s Ϫ1 ·mg Ϫ1 ww) and a tighter coupling of oxidative phosphorylation. In RTA, the greater muscle mass and maximal force and the enhanced mitochondrial respiration seem to compensate for the hypertrophy-induced impaired peripheral O2 diffusion. The net results are an enhanced whole body oxidative function at peak exercise and unchanged efficiency and O 2 cost at submaximal exercise, despite a much greater body mass. skeletal muscle hypertrophy; mitochondrial respiration; oxidative metabolism during exercise RESISTANCE TRAINING PROGRAMS have been developed with the aim of improving variables of muscle function such as strength, power, speed, local muscular endurance, coordination, and flexibility (21). Resistance training is now considered an important part of training and rehabilitation programs for healthy subjects and for various types of patients, such as cardiac patients (45), patients with pulmonary diseases (10), patients undergoing prolonged bed-rest periods (2), or elderly subjects (28). In these populations, the combination of resistance training with the more conventional endurance exercise improves the patients' outcomes and quality of life (45).An increase in the cross-sectional area of skeletal muscle fibers and a shift of fiber-type distribution toward type 2 fibers are typical adaptations induced by resistance training; these adaptations enhance the muscle force-generating potential (12) but could represent an impairment to skeletal muscle oxidative metabolism. On the other hand, muscles with higher maximal force would need to recruit a lower number of motor units, and therefore more oxidative (and more efficient) muscle fibers (20,26). According to other authors, strength training may increas...

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Section: Methodological Considerationssupporting

confidence: 91%

Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Salvadego

Domenis

Lazzer

et al. 2013

Journal of Applied Physiology

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“…Muscle samples were incubated in the presence of different concentrations of insulin (0, 4, 40 and 100 nmol/l) in the preservation medium for 2.5 h, then permeabilised using saponin, and rinsed using respiration medium as described previously [2,3,21].…”

Section: Methodsmentioning

confidence: 99%

“…To overcome the possibility of limited muscle glucose transport despite hyperinsulinaemic conditions in patients with type 2 diabetes, the effect of insulin on fATP was also measured under hyperglycaemic conditions to match the insulin-induced increase in intramyocellular glucose 6-phosphate observed in non-diabetic humans [7]. Interestingly, even hyperglycaemia did not restore the stimulatory effect of insulin on fATP in these patients, suggesting intrinsic mitochondrial abnormalities as previously suggested [2,3,14].…”

Section: Introductionmentioning

confidence: 99%

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Reduction of non-esterified fatty acids improves insulin sensitivity and lowers oxidative stress, but fails to restore oxidative capacity in type 2 diabetes: a randomised clinical trial

et al. 2013

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Aims/hypothesis Muscle mitochondrial function can vary during fasting, but is lower during hyperinsulinaemia in insulinresistant humans. Ageing and hyperlipidaemia may be the culprits, but the mechanisms remain unclear. We hypothesised that (1) insulin would fail to increase mitochondrial oxidative capacity in non-diabetic insulin-resistant young obese humans and in elderly patients with type 2 diabetes and (2) reducing NEFA levels would improve insulin sensitivity by raising oxidative capacity and lowering oxidative stress. Methods Before and after insulin (4, 40, 100 nmol/l) stimulation, mitochondrial oxidative capacity was measured in permeabilised fibres and isolated mitochondria using highresolution respirometry, and H 2 O 2 production was assessed fluorimetrically. Tissue-specific insulin sensitivity was measured with hyperinsulinaemic-euglycaemic clamps combined with stable isotopes. To test the second hypothesis, in a 1-day randomised, crossover study, 15 patients with type 2 diabetes recruited via local advertisement were assessed for eligibility. Nine patients fulfilled the inclusion criteria (BMI <35 kg/m 2 ; age <65 years) and were allocated to and completed the intervention, including oral administration of 750 mg placebo or acipimox. Blinded randomisation was performed by the pharmacy; all participants, researchers performing the measurements and those assessing study outcomes were blinded. The main outcome measures were insulin sensitivity, oxidative capacity and oxidative stress. Results Insulin sensitivity and mitochondrial oxidative capacity were ∼31% and ∼21% lower in the obese groups than in the lean group. The obese participants also exhibited blunted substrate oxidation upon insulin stimulation. In the patients with type 2 diabetes, acipimox improved insulin sensitivity by ∼27% and reduced H 2 O 2 production by ∼45%, but did not improve basal or insulin-stimulated mitochondrial oxidative capacity. No harmful treatment side effects occurred. Conclusions/interpretation Decreased mitochondrial oxidative capacity can also occur independently of age in insulinresistant young obese humans. Insulin resistance is present at the muscle mitochondrial level, and is not affected by reducing circulating NEFAs in type 2 diabetes. Thus, impaired plasticity of mitochondrial function is an intrinsic phenomenon that probably occurs independently of lipotoxicity and reduced glucose uptake.

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“…The recognition that mitochondria may play a central role in disease has renewed interest in the Randle cycle and the Warburg effect in the pathogenesis of common diseases [5,6], and may be relevant because the inefficient use of glucose, lipotoxicity, and decreased fat oxidation are key mechanisms to explain most noncommunicable diseases [7,8]. Consequently, the pharmacologic modulation of mitochondrial function mimicking the effect of exercise and/or caloric restriction may be an attractive therapeutic strategy [9,10].…”

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confidence: 99%

Exploring the Process of Energy Generation in Pathophysiology by Targeted Metabolomics: Performance of a Simple and Quantitative Method

Riera-Borrull

Rodríguez-Gallego

Hernández-Aguilera

et al. 2015

J. Am. Soc. Mass Spectrom.

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Abstract. Abnormalities in mitochondrial metabolism and regulation of energy balance contribute to human diseases. The consequences of high fat and other nutrient intake, and the resulting acquired mitochondrial dysfunction, are essential to fully understand common disorders, including obesity, cancer, and atherosclerosis. To simultaneously and noninvasively measure and quantify indirect markers of mitochondrial function, we have developed a method based on gas chromatography coupled to quadrupole-time of flight mass spectrometry and an electron ionization interface, and validated the system using plasma from patients with peripheral artery disease, human cancer cells, and mouse tissues. This approach was used to increase sensibility in the measurement of a wide dynamic range and chemical diversity of multiple intermediate metabolites used in energy metabolism. We demonstrate that our targeted metabolomics method allows for quick and accurate identification and quantification of molecules, including the measurement of small yet significant biological changes in experimental samples. The apparently low process variability required for its performance in plasma, cell lysates, and tissues allowed a rapid identification of correlations between interconnected pathways. Our results suggest that delineating the process of energy generation by targeted metabolomics can be a valid surrogate for predicting mitochondrial dysfunction in biological samples. Importantly, when used in plasma, targeted metabolomics should be viewed as a robust and noninvasive source of biomarkers in specific pathophysiological scenarios.

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Exercise training increases mitochondrial content and ex vivo mitochondrial function similarly in patients with type 2 diabetes and in control individuals

Cited by 178 publications

References 22 publications

Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Reduction of non-esterified fatty acids improves insulin sensitivity and lowers oxidative stress, but fails to restore oxidative capacity in type 2 diabetes: a randomised clinical trial

Exploring the Process of Energy Generation in Pathophysiology by Targeted Metabolomics: Performance of a Simple and Quantitative Method

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