Håkan Westerblad

The common ACTN3 R577X polymorphism leads to α‐actinin‐3 deficiency in ~20% of the human population and may be detrimental to their muscle power. However, the impact of ACTN3 R577X on metabolic health and exercise capacity in the general population remains unclear. The objective of the current study was to compare metabolic health markers, musculoskeletal traits, and cardiorespiratory capacity between untrained overweight α‐actinin‐3‐deficient (XX; 20 men and 19 women) and α‐actinin‐3 expressing (RR; 20 men and 21 women) individuals. The participants were aged 43 ± 7 years and had a BMI of 28.6 ± 3.2 kg·m ⁻² . Various metabolic health and exercise capacity aspects encompassing segmental body composition, bone density, systemic low‐grade inflammation, blood lipid profile, whole‐body glucose tolerance and insulin sensitivity, resting and exercise metabolism, and exercise capacity were evaluated. While XX groups had lower fat‐free mass than RR groups, other anthropometrical and body composition features, including bone mineral content, did not differ between the genotype groups in either women or men. We found no significant differences between XX and RR individuals for blood lipid profile, markers of systemic inflammation, glucose tolerance, resting metabolism, and leg strength. Moreover, no clear genotype‐related differences were observed in markers of insulin resistance and sensitivity, although XX women exhibited a slightly smaller increase in insulin concentration than RR women during an oral glucose tolerance test. An incremental cardiopulmonary cycling test revealed no differences in metabolic and heart rate responses, maximal fat oxidation, or exercise capacity. In conclusion, we observed no associations between α‐actinin‐3 deficiency and metabolic health, body composition, muscle function, or cardiorespiratory capacity in untrained overweight men and women.

Sprint interval training (SIT) is a time‐efficient type of endurance training that involves large type 2 muscle fibre recruitment. Effective antioxidant supplementation may mitigate positive training adaptations by limiting the oxidant challenge. Our aim was to test whether SIT affects type 2 more than type 1 muscle fibres, and whether the muscular training response is mitigated by antioxidant treatment. Young men performed three weekly SIT sessions (4–6 × 30 s all‐out cycling) for 3 weeks while treated with antioxidants (vitamin C, 1 g day⁻¹; vitamin E, 235 mg day⁻¹) or placebo. Vastus lateralis biopsies were taken to measure (i) activation of genes for reactive oxygen/nitrogen species (ROS) sensors and inflammatory mediators with quantitative RT‐PCR and (ii) fibre type‐specific proteome adaptations using MS‐based proteomics. Vitamin treatment decreased the upregulation of genes for ROS sensors and inflammatory regulators during the first SIT session. The 3 weeks of SIT caused generally larger proteome adaptations in type 2 than in type 1 fibres, and this included larger increases in abundance of proteins involved in mitochondrial energy production. Vitamin treatment blunted the SIT‐induced proteome adaptations, whereas it did not affect the training‐induced improvement in maximal cycling performance. In conclusion, (i) the large type 2 fibre recruitment and resulting proteome adaptations are instrumental to the effectiveness of SIT and (ii) antioxidant supplementation counteracts positive muscular adaptations to SIT, which would blunt any improvement in submaximal endurance performance, whereas it does not affect the improvement in maximal cycling performance, where O₂ delivery to muscle would be limiting. image Key points: Sprint interval training (SIT) is a time‐efficient type of endurance training that involves large recruitment of fast‐twitch muscle fibres. Treatment with antioxidants may mitigate the positive effects of endurance training. Fibre type‐specific proteomics performed on muscle biopsies obtained from young men before and after 3 weeks of SIT showed larger training effects in fast‐ than in slow‐twitch fibres. Antioxidant treatment in the form of vitamin C and E pills counteracted the positive muscular adaptations to the 3 weeks of SIT. These results increase our understanding of why SIT is an effective endurance training regime and provide further evidence against the common belief that antioxidant supplements are beneficial in a physical exercise context.

Sprint interval training (SIT) is a time-efficient type of endurance training that involves large type 2 muscle fibre recruitment. Effiective antioxidant supplementation may mitigate positive training adaptations by limiting the oxidant challenge. Our aim was to test whether SIT affiects type 2 more than type 1 muscle fibres, and whether the training response is mitigated by antioxidant treatment. Young men performed three SIT sessions (6 × 30 s all-out cycling) per week for three weeks while treated with antioxidants (vitamin C, 1 g/day; vitamin E, 235 mg/day) or placebo. Vastus lateralis biopsies were taken to measure (i) activation of genes for reactive oxygen/nitrogen species (ROS) sensors and inflammatory mediators with quantitative RT PCR and (ii) fibre type-specific proteome adaptations using mass spectrometry-based proteomics. Vitamin treatment decreased the upregulation of genes for ROS sensors and inflammatory regulators during the first SIT session. The three weeks of SIT caused generally larger proteome adaptations in type 2 than in type 1 fibres, and this included larger increases in abundance of proteins involved in mitochondrial energy production. Vitamin treatment blunted the SIT-induced proteome adaptations, whereas it did not affiect the training-induced improvement in maximal cycling performance. In conclusion, (i) the large type 2 fibre recruitment and resulting proteome adaptations are instrumental to the effiectiveness of SIT, and (ii) antioxidant supplementation counteracts positive muscular adaptations to SIT, which would blunt any improvement in submaximal endurance performance, whereas it does not affiect the improvement in maximal cycling performance, where O2 delivery to muscle would be limiting.

Objective: To investigate efficacy, safety, and tolerance of high-intensity interval training (HIIT) versus standard low-moderate intensity home-based exercise (CON) to improve aerobic capacity, muscle endurance, and mitochondrial function in patients with recent onset, idiopathic inflammatory myopathies (IIM). Methods: Twenty-three patients with recent onset IIM were randomized into two groups: HIIT and CON. HIIT underwent 12 weeks of supervised high-intensity training, while CON followed a low-moderate intensity home-based exercise program. Outcomes included maximal exercise test (VO ₂ peak, peak power, time-to-exhaustion (TTE)), mitochondrial protein expression in muscle biopsy serum levels of muscle enzymes (CK, LD, AST, ALT), muscle strength (MMT8) and disease activity (subset of MDAAT), before and after intervention. Results: HIIT resulted in a 16 % increase in VO ₂ peak L/min, significantly higher than the 1.8 % change in CON (95 % CI 0.1;0.47). Peak power and TTE also improved significantly more in HIIT, 18 % and 23 %, respectively, compared to CON, 8 % and 12 %, (95 % CI 3.9;30.8 and 00:06;03:18, respectively). Muscle biopsies (HIIT n=7, CON n=6) showed increases (p The study was registered at ClinicalTrials.gov : NCT03324152 Significance and Innovations: High-intensity interval training (HIIT) is more effective to improve aerobic capacity (peak oxygen uptake; VO ₂ peak), increasing 16 % compared to 1.8 % change in the moderate exercise control group in patients with recent onset IIM. HIIT produced larger exercise adaptations with increased expression of aerobic metabolism (mitochondrial) proteins in muscle tissue compared to moderate exercise. HIIT is a safe and well tolerated exercise intervention for patients with recent onset IIM.

Skeletal muscle fibers need to have mechanisms to decrease energy consumption during intense physical exercise to avoid devastatingly low ATP levels, with the formation of rigor cross bridges and defective ion pumping. These protective mechanisms inevitably lead to declining contractile function in response to intense exercise, characterizing fatigue. Through our work, we have gained insights into cellular and molecular mechanisms underlying the decline in contractile function during acute fatigue. Key mechanistic insights have been gained from studies performed on intact and skinned single muscle fibers and more recently from studies performed and single myosin molecules. Studies on intact single fibers revealed several mechanisms of impaired sarcoplasmic reticulum Ca²⁺ release and experiments on single myosin molecules provide direct evidence of how putative agents of fatigue impact myosin’s ability to generate force and motion. We conclude that changes in metabolites due to an increased dependency on anaerobic metabolism (e.g., accumulation of inorganic phosphate ions and H⁺) act to directly and indirectly (via decreased Ca²⁺ activation) inhibit myosin’s force and motion-generating capacity. These insights into the acute mechanisms of fatigue may help improve endurance training strategies and reveal potential targets for therapies to attenuate fatigue in chronic diseases.