Jørn W. Helge’s research while affiliated with IT University of Copenhagen and other places

It is not clear if fat oxidation is attenuated at higher exercise intensities, when exercising with a small muscle mass, and therefore, we studied leg fat oxidation during graded one‐leg exercise. Ten males (age: 27 ± 2 years, body mass: 82 ± 3 kg, BMI: 24 ± 1 kg m⁻², V̇O2max: 49 ± 2 mL min⁻¹ kg⁻¹) performed one‐leg exercise at 25% of maximal workload (Wmax) for 30 min, followed by 120‐min exercise at 55% Wmax with the contralateral leg, and finally 30‐min exercise at 85% Wmax with the first leg. Blood was sampled from an artery and both femoral veins, and blood flow was determined using Doppler ultrasound. Muscle biopsies were obtained before and after 30 min at each workload. One‐way RM ANOVA was applied to determine the impact of exercise intensity. Data are expressed as mean ± SEM. From rest through exercise average blood flow (0.4 ± 0.1, 2.1 ± 0.1, 2.6 ± 0.2, 3.7 ± 0.2 L min⁻¹) and oxygen uptake across the leg (0.03 ± 0.01, 0.23 ± 0.02, 0.35 ± 0.03, 0.53 ± 0.04 L min⁻¹) increased with exercise intensity (p < 0.001). Leg RQ (0.76 ± 0.04, 0.86 ± 0.02,0.87 ± 0.01, 0.92 ± 0.01, p < 0.001), leg plasma FA uptake (2 ± 2, 46 ± 8,83 ± 9, 114 ± 16 μmol min⁻¹; p < 0.001) and rate of leg fat oxidation (0.016 ± 0.005, 0.062 ± 0.012, 0.075 ± 0.011, 0.084 ± 0.018 g min⁻¹, p < 0.007) increased with exercise intensity. Muscle‐free carnitine content was unchanged from rest at 25% Wmax and decreased after 30 min exercise at 55% and 85% Wmax (17.4 ± 1.6, 16.6 ± 0.7, 14.5 ± 1.2, 10.5 ± 1.0 mmol/kg dry muscle, respectively; p < 0.006). During incremental one‐leg exercise, the rate of leg fat oxidation was not attenuated with increasing exercise intensity, probably due to an insufficient muscle metabolic stress response.

Type 2 diabetes (T2D) is associated with vascular endothelial dysfunction and microvascular rarefaction in skeletal muscle tissue (1). Although endothelial dysfunction in metabolic disease is proposed to be associated with altered endothelial cell metabolism, there is to date a paucity of human data to support this notion. The aim of this study was to investigate the metabolism in microvascular endothelial cells derived from skeletal muscle biopsies. Moreover, as exercise training is known to reverse endothelial dysfunction and promote angiogenesis, the effect of a period of exercise training was assessed. Microvascular endothelial cells were isolated from m. vastus lateralis biopsies taken from obese individuals with (n = 7) and without (n = 8) T2D before and after 12 weeks of aerobic exercise training. Mitochondrial respiration, hydrogen peroxide (H 2 O 2 ) emission, and nitric oxide (NO) formation were determined in the cells by the Oroboros Oxygraph-2K. In addition, angiogenic-, metabolic- and antioxidant enzymes and proteins, cell proliferation, and skeletal muscle capillarization were determined. At baseline, there was no difference between endothelial cells from obese control participants and T2D obese participants for any of the parameters measured: glycolytic capacity, as evidenced by a similar lactate production and PFK-1 protein content, respiratory capacity, H 2 O 2 emission, NO emission, endothelial NO synthase protein (eNOS) content. The training period led to an overall increase in the respiratory capacity in endothelial cells from both groups (main effect, P = 0.021) whereas mitochondrial H 2 O 2 emission remained unaltered. There was no change in glycolytic capacity, superoxide dismutase 2 or eNOS protein contents, or NO emission. Training did not influence the capillary-to-muscle fiber ratio in either group. The results of this study show that aerobic exercise training of obese control and obese diabetic subjects leads to an increase in the respiratory capacity of muscle microvascular endothelial cells. The data also indicate that there are no differences in endothelial metabolism and NO production between obese control and obese diabetic individuals. However, as the study is ongoing and only half of the subjects have been included at this time, power is limited and results may differ upon completion. Data from all subjects will be presented at the conference. Funding: The study is funded by Novo Nordisk A/S. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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% VO 2 peak). 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.

The fat oxidation capacity is higher in young compared to elderly subjects and higher in premenopausal compared to postmenopausal women, but the influence of age on maximal fat oxidation (MFO) is not clear. Therefore, this study aimed to evaluate MFO (g/min) across the lifespan of trained adult women. In total, 36 healthy trained women were recruited into three groups: (n = 12), young (27 ± 3 years, mean ± SD) premenopausal, middle‐aged (57 ± 3 years), and older (71 ± 2 years) postmenopausal women and all had a body mass index <25 kg/m². After an overnight fast, body composition was determined by dual‐energy X‐ray absorptiometry, and blood samples were obtained. A FATmax‐test was performed on a cycle ergometer, and MFO was calculated from the pulmonary V̇O2 and V̇CO2 measured by indirect calorimetry. The absolute MFO was significantly higher in young (0.40 ± 0.07 g/min) compared to both middle‐aged (0.33 ± 0.07 g/min) (p = 0.035) and old (0.25 ± 0.05 g/min) women (p < 0.001). Absolute MFO was higher in middle‐aged compared to old women (p = 0.018). Relative MFO (MFO/LBM, mg/min/LBM) was higher in young (8.39 ± 1.62 mg/min/LBM) compared to old (6.16 ± 1.14 mg/min/LBM) women (p = 0.004). A significant linear relationship was observed between absolute MFO and age (R² = 0.41; p < 0.001), V̇O2max (R² = 0.40; p < 0.001), and LBM (R² = 0.13; p = 0.033), respectively, and between relative MFO and fat mass (R² = 0.12; p = 0.04). In conclusion, the maximal capacity to oxidize fat is attenuated with age in trained women. Furthermore, postmenopausal middle‐aged women have higher absolute MFO compared to older women, and this implies that it is age per se and not a change in estrogen availability that leads to lower absolute MFO.

Background Low cardiorespiratory fitness (ie, peak oxygen consumption [V.O2peak]) is associated with cardiovascular disease and all-cause mortality and is recognized as an important clinical tool in the assessment of patients. Cardiopulmonary exercise test (CPET) is the gold standard procedure for determination of V.O2peak but has methodological challenges as it is time-consuming and requires specialized equipment and trained professionals. Seismofit is a chest-mounted medical device for estimating V.O2peak at rest using seismocardiography. Objective The purpose of this study was to investigate the validity and reliability of Seismofit V.O2peak estimation in a healthy population. Methods On 3 separate days, 20 participants (10 women) underwent estimations of V.O2peak with Seismofit (×2) and Polar Fitness Test (PFT) in randomized order and performed a graded CPET on a cycle ergometer with continuous pulmonary gas exchange measurements. Results Seismofit V.O2peak showed a significant bias of –3.1 ± 2.4 mL·min–1·kg–1 (mean ± 95% confidence interval) and 95% limits of agreement (LoA) of ±10.8 mL·min–1·kg–1 compared to CPET. The mean absolute percentage error (MAPE) was 12.0%. Seismofit V.O2peak had a coefficient of variation of 4.5% ± 1.3% and an intraclass correlation coefficient of 0.95 between test days and a bias of 0.0 ± 0.4 mL·min–1·kg–1 with 95% LoA of ±1.6 mL·min–1·kg–1 in test–retest. In addition, Seismofit showed a 2.4 mL·min–1·kg–1 smaller difference in 95% LoA than PFT compared to CPET. Conclusion The Seismofit is highly reliable in its estimation of V.O2peak. However, based on the measurement error and MAPE >10%, the Seismofit V.O2peak estimation model needs further improvement to be considered for use in clinical settings.

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.

Background: Statin therapy has shown pleiotropic effects affecting both mitochondrial function and inflammatory status. However, few studies have investigated the concurrent effects of statin exposure on mitochondrial function and inflammatory status in human subcutaneous white adipose tissue. Objectives: In a cross-sectional study, we investigated the effects of simvastatin on mitochondrial function and inflammatory status in subcutaneous white adipose tissue of 55 human participants: 38 patients (19 female/19 male) in primary prevention with simvastatin (> 40 mg/day, > 3 mo) and 17 controls (9 female/8 male) with elevated plasma cholesterol. The two groups were matched on age, BMI and VO2max. Methods: Anthropometrics and fasting biochemical characteristics were measured. Mitochondrial respiratory capacity was assessed in white adipose tissue by high-resolution respirometry. Subcutaneous white adipose tissue expression of the inflammatory markers IL-6, CCL-2, CCL-5, TNFα, IL-10 and IL-4 was analysed by qPCR. Results: Simvastatin-treated patients showed lower plasma cholesterol (p < 0.0001), LDL (p < 0.0001) and triglyceride levels (p = 0.0116) than controls. Simvastatin-treated patients had a lower oxidative phosphorylation capacity of mitochondrial complex II (p = 0.0001 when normalised to wet weight, p < 0.0001 when normalised to citrate synthase activity (intrinsic)) and a lower intrinsic mitochondrial electron transport system capacity (p = 0.0004). Simvastatin-treated patients showed higher IL-6 expression than controls (p = 0.0202). Conclusion: Simvastatin treatment was linked to mitochondrial respiratory capacity in human subcutaneous white adipose tissue, but no clear link was found between statin exposure, respiratory changes and inflammatory status of adipose tissue.

Objectives: Traditional jumping-dance rituals performed by Maasai men involve prolonged physical exertion that may contribute significantly to overall physical activity level. We aimed to objectively quantify the metabolic intensity of jumping-dance activity and assess associations with habitual physical activity and cardiorespiratory fitness (CRF). Methods: Twenty Maasai men (18-37 years) from rural Tanzania volunteered to participate in the study. Habitual physical activity was monitored using combined heart rate (HR) and movement sensing over 3 days, and jumping-dance engagement was self-reported. A 1-h jumping-dance session resembling a traditional ritual was organized, during which participants' vertical acceleration and HR were monitored. An incremental, submaximal 8-min step test was performed to calibrate HR to physical activity energy expenditure (PAEE) and assess CRF. Results: Mean (range) habitual PAEE was 60 (37-116) kJ day-1 kg-1 , and CRF was 43 (32-54) mL O2 min-1 kg-1 . The jumping-dance activity was performed at an absolute HR of 122 (83-169) beats·min-1 , and PAEE of 283 (84-484) J min-1 kg-1 or 42 (18-75)% when expressed relative to CRF. The total PAEE for the session was 17 (range 5-29) kJ kg-1 , ~28% of the daily total. Self-reported engagement in habitual jumping-dance frequency was 3.8 (1-7) sessions/week, with a total duration of 2.1 (0.5-6.0) h/session. Conclusions: Intensity during traditional jumping-dance activity was moderate, but on average sevenfold higher than habitual physical activity. These rituals are common, and can make a substantial contribution to overall physical activity in Maasai men, and thus be promoted as a culture-specific activity to increase energy expenditure and maintain good health in this population.