Arthur Ingersen

The interindividual variability in peak fat oxidation (PFO) and the intensity at which this occurs (Fat _max ) has been attributed to physiological factors, diet and physical activity; however, few studies have examined the contribution of skeletal muscle characteristics. The present study examined the relationship between PFO, Fat _max and the skeletal muscle proteome in young, physically active males. Thirty‐four young, lean males were phenotyped through assessment of aerobic capacity, PFO, body composition, fasting blood samples and a muscle biopsy. Liquid chromatography mass spectrometry based proteomics was used to assess skeletal muscle protein abundance. Only absolute PFO (g min ⁻¹ ) was positively correlated with ( r = 0.496, P =  0.003). Few skeletal muscle proteins correlated with absolute PFO, whereas relative PFO and Fat _max were positively associated with numerous mitochondrial proteins enriched in metabolic pathways, oxidative phosphorylation and other mitochondrial processes. Mitochondrial proteome abundance was positively correlated with both relative PFO ( r = 0.633, P <  0.001) and Fat _max ( r = 0.595, P <  0.001). Mitochondrial complex‐specific analysis demonstrated that respiratory complex V was associated with both relative PFO and Fat _max . Multiple regression analyses indicated that mitochondrial abundance and muscle glycogen explained 55% of the variability in relative PFO, whereas mitochondrial abundance alone explained 43% of the variability in Fat _max . Absolute PFO was explained by a combination of , mitochondrial abundance and muscle glycogen content ( r ² = 0.562). This untargeted proteomic approach highlights that skeletal muscle mitochondrial content contributes to the interindividual variability in PFO and Fat _max in lean, active young males. image Key points: This study used an untargeted proteomics approach to explore the links between the skeletal muscle proteome and peak fat oxidation (PFO) in young, physically active males. Absolute PFO was primarily associated with maximal aerobic capacity. When expressed relative to fat‐free mass, PFO was closely associated with skeletal muscle proteins enriched in oxidative metabolism and mitochondrial pathways. Mitochondrial abundance assessed by mitochondrial proteome content and citrate synthase activity was positively related to relative PFO and the intensity at which this occurs (Fat _max ). Mitochondrial respiratory complex V was consistently related to both relative PFO and Fat _max . Mitochondrial content independently contributed to both PFO and Fat _max , highlighting mitochondrial content as a key determinant of the maximal capacity for fat oxidation.

Purpose: This study aimed to investigate the validity and applicability of a non-exercise estimation of cardiorespiratory fitness using resting seismocardiography (SCG eV̇O₂peak) in people with overweight and obesity before and after a 14-week lifestyle intervention. Methods: The study was carried out at a Folk high school that offers 14-week courses on lifestyle changes where participants live at the school and voluntarily participate in daily lectures and activities. Sixty-seven men and women with age and body mass index between 18 and 70 years and 25–50 kg·m^–2 were tested at baseline, and 52 had a follow-up test after 14 weeks. Testing included the determination of anthropometric variables, an SCG eV̇O₂peak at supine rest, and a gold standard V̇O₂peak test on a cycle ergometer until voluntary exhaustion. Results: Agreement analysis for V̇O₂peak at baseline (n = 67, SCG eV̇O₂peak: 26.9 ± 1.9 ml·min^–1·kg^–1, V̇O₂peak: 26.6 ± 1.6 ml·min^–1·kg^–1, mean ± 95% confidence interval) showed a bias of 0.3 ± 1.0 ml·min^–1·kg^–1 with 95% limits of agreement (LoA) ranging ± 9.8 ml·min^–1·kg^–1. A Pearson’s correlation of r = 0.78 (p < 0.0001) and a standard error of estimate (SEE) of 5.0 ml·min^–1·kg^–1 were found between methods. At follow-up (n = 52), body mass was reduced by 6.6 ± 1.4 kg (p < 0.0001). V̇O₂peak increased by 3.3 ± 0.9 ml·min^–1·kg^–1 and 175 ± 78 ml·min^–1 and SCG eV̇O₂peak by 2.6 ± 0.8 ml·min^–1·kg^–1 and 93 ± 76 ml·min^–1 (two-way ANOVA repeated measure: intervention p < 0.0001, method p = 0.939 and interaction p = 0.125, relative V̇O₂peak). A Pearson’s correlation of r = 0.37 (p < 0.05) was found between changes in relative V̇O₂peak but not for absolute V̇O₂peak r = 0.10 (p = 0.402). Conclusions: The SCG method is accurate for estimating V̇O₂peak and appropriate for detecting group changes in both relative and absolute V̇O₂peak following a lifestyle intervention in people with overweight and obesity. Furthermore, the method can detect individual changes in V̇O₂peak but not independently of body mass changes. Yet, the applicability is still limited by the relatively large variation in LoA and SEE.

Aim: To investigate effects of hormone replacement therapy in postmenopausal women on factors associated with metabolic flexibility related to whole‐body parameters including fat oxidation, resting energy expenditure, body composition and plasma concentrations of fatty acids, glucose, insulin, cortisol, and lipids, and for the mitochondrial level, including mitochondrial content, respiratory capacity, efficiency, and hydrogen peroxide emission.Methods: 22 postmenopausal women were included. 11 were undergoing estradiol and progestin treatment (HT), and 11 were matched non‐treated controls (CONT). Peak oxygen consumption, maximal fat oxidation, glycated hemoglobin, body composition, and resting energy expenditure were measured. Blood samples were collected at rest and during 45 min of ergometer exercise (65% VO₂peak). Muscle biopsies were obtained at rest and immediately post‐exercise. Mitochondrial respiratory capacity, efficiency, and hydrogen peroxide emission in permeabilized fibers and isolated mitochondria were measured, and citrate synthase (CS) and 3‐hydroxyacyl‐CoA dehydrogenase (HAD) activity were assessed.Results: HT showed higher absolute mitochondrial respiratory capacity and post‐exercise hydrogen peroxide emission in permeabilized fibers and higher CS and HAD activities. All respiration normalized to CS activity showed no significant group differences in permeabilized fibers or isolated mitochondria. There were no differences in resting energy expenditure, maximal, and resting fat oxidation or plasma markers. HT had significantly lower visceral and total fat mass compared to CONT.Conclusion: Use of hormone therapy is associated with higher mitochondrial content and respiratory capacity and a lower visceral and total fat mass. Resting energy expenditure and fat oxidation did not differ between HT and CONT.

Background The aim was to investigate the effect of prolonged endurance exercise on adipose tissue inflammation markers and mitochondrial respiration in young and old men. Methods Young (aged 30 years, n = 7) and old (aged 65 years, n = 7) trained men were exposed to an exercise intervention of 15 consecutive days biking 7-9 hours/day at 63% and 65% of maximal heart rate (young and old, respectively), going from Copenhagen, Denmark to Palermo, Italy. Adipose tissue was sampled from both the gluteal and abdominal depot before and after the intervention. Mitochondrial respiration was measured by high-resolution respirometry and adipose inflammation was assessed by immunohistochemical staining of paraffin embedded sections. Results An increased number of CD163 + macrophages was observed in both the gluteal and abdominal depot (P < 0.01). In addition, an increased mitochondrial respiration was observed in the abdominal adipose tissue from the young group with complex I (CI_p) stimulated respiration, complex I + II (CI + II_p) stimulated respiration and the capacity of the electron transport system (ETS)(P < 0.05), and in the old group an increase in CI_p and CI + II_p stimulated respiration (P < 0.05) was found. Conclusion Overall, we found a positive effect of prolonged endurance exercise on adipose tissue inflammation markers and mitochondrial respiration in both young and old trained men, and no sign of attenuated function in AT with age.

Context: Prior to this study, it is known that type 2 diabetes is linked to obesity and a sedentary lifestyle, leading to inadequate β-cell function and insulin resistance. Limited research has explored the metabolic effects of combining exercise training with antidiabetic medications, particularly focusing on insulin secretion in patients with type 2 diabetes and moderately preserved β-cell function. Objective: The effect of the interaction of semaglutide and physical training on pancreatic β-cell secretory function is unknown in patients with type 2 diabetes. Methods: Thirty-one patients with type 2 diabetes underwent 12 weeks of aerobic training alone or concurrent to treatment with semaglutide. Patients randomly allocated to concurrent semaglutide and training were treated with semaglutide for 20 weeks before the training and evaluated at inclusion and again before and after the training intervention. Patients randomized to training were evaluated before and after training. The primary outcome was a change in insulin secretory capacity with training, evaluated by a 2-stepped hyperglycemic (20 and 30 mM) clamp. Results: Training increased the incremental area under the curve for insulin from 21 to 27 nM × 2 hours (ratio 1.28, 95% CI 1.02-1.60) during clamp step 1 and from 40 to 64 nM × 2 hours (ratio 1.61, 95% CI 1.25-2.07) during step 2. Semaglutide treatment increased insulin secretion from 16 to 111 nM × 2 hours (ratio 7.10, 95% CI 3.68-13.71), and from 35 to 447 nM × 2 hours (ratio 12.74, 95% CI 5.65-28.71), correspondingly. Semaglutide and training increased insulin secretion from 130 to 171 nM × 2 hours (ratio 1.31, 95% CI 1.06-1.63), and from 525 to 697 nM × 2 hours (ratio 1.33, 95% CI 1.02-1.72), correspondingly. The median increase in total insulin secretion with the combination was 134 nM × 2 hours greater (95% CI 108-232) than with training. Conclusion: The combination of aerobic training and semaglutide treatment synergistically improved β-cell secretory function. (ClinicalTrials.gov number, ID NCT04383197).

It has recently been established that myosin, the molecular motor protein, is able to exist in two conformations in relaxed skeletal muscle. These conformations are known as the super-relaxed (SRX) and disordered-relaxed (DRX) states and are finely balanced to optimize ATP consumption and skeletal muscle metabolism. Indeed, SRX myosins are thought to have a 5- to 10-fold reduction in ATP turnover compared with DRX myosins. Here, we investigated whether chronic physical activity in humans would be associated with changes in the proportions of SRX and DRX skeletal myosins. For that, we isolated muscle fibers from young men of various physical activity levels (sedentary, moderately physically active, endurance-trained, and strength-trained athletes) and ran a loaded Mant-ATP chase protocol. We observed that in moderately physically active individuals, the amount of myosin molecules in the SRX state in type II muscle fibers was significantly greater than in age-matched sedentary individuals. In parallel, we did not find any difference in the proportions of SRX and DRX myosins in myofibers between highly endurance- and strength-trained athletes. We did however observe changes in their ATP turnover time. Altogether, these results indicate that physical activity level and training type can influence the resting skeletal muscle myosin dynamics. Our findings also emphasize that environmental stimuli such as exercise have the potential to rewire the molecular metabolism of human skeletal muscle through myosin.