ECSS Paris 2023: OP-PN23
INTRODUCTION: To generate 1 g of dry biomass, hypertrophying skeletal muscles must take up 1 g of metabolites from the circulation. While much of this uptake is expected to consist of amino acids for protein synthesis, little is known about which of the ~200,000 metabolites detected in humans (HMDB data) are taken up or released during muscle growth. To gain insight into global metabolite exchange during skeletal muscle hypertrophy, we profiled metabolite uptake and release in IGF-1-stimulated C2C12 myotubes and in the human leg 24 h following resistance exercise compared with unstimulated controls. METHODS: Differentiated C2C12 myotubes were growth-stimulated with IGF-1 (100ng/ml, 24 h) or received vehicle control. To measure metabolite exchange, we analyzed fresh and spent media by GC-MS metabolomics. In a second experiment, seven untrained adults (3 males, 4 females; age 25.6 ± 3.2 years; BMI 23.8 ± 2.8 kg·m⁻²) performed single-leg hypertrophy-oriented resistance exercise, with the contralateral leg serving as control. After 24 h, we obtained femoral arterial and venous blood samples under fasting conditions and analyzed plasma by untargeted LC-MS metabolomics to quantify net muscle metabolite exchange. RESULTS: Compared with controls, IGF-1-treated myotubes took up more serine (log2FC = −1.73, p < 0.001), arginine (−0.58, p = 0.017), and pyridoxamine (−0.9, p = 0.017), and released more lactate into the culture medium (+0.72, p < 0.001), consistent with anabolic, Warburg-like metabolic reprogramming. Upon IGF-1 stimulation, we detected increased uptake of metabolites linked to central carbon metabolism and cofactor biosynthesis. In contrast, untargeted human arteriovenous metabolomics revealed only modest differences in global metabolite exchange between the exercised and contralateral control leg (PCA PC1 8.8%, PC2 6.3% variance explained). We observed no significant increase in essential amino acid uptake 24 h post-exercise. Nevertheless, 15 metabolites differed between legs, with the exercised muscle preferentially taking up amino acid and peptide-related metabolites (acisoga, 2-amino-4-CP), palmitic acid, and α-ketoglutarate, while releasing lipid-derived intermediates including C12:0 and C16:0 acylcarnitines. However, none of these differences persisted after FDR correction. CONCLUSION: IGF-1 stimulation in vitro promotes a coordinated uptake of nitrogen-rich metabolites and increased lactate release, reflecting a cancer-like metabolic reprogramming. In contrast, metabolite exchange in fasted human muscle 24 h after resistance exercise is characterized by increased peptide turnover and lipid intermediate release rather than net amino acid uptake, indicating limited substrate accumulation and net biomass accretion in the absence of exogenous nutrients.
Read CV Moritz EggelbuschECSS Paris 2023: OP-PN23
INTRODUCTION: Whole-body fat oxidation correlates with mitochondrial oxidative capacity, emphasising the role of mitochondrial function in systemic and skeletal muscle substrate utilisation during exercise – a relationship that may be modulated by the prevailing fuel availability (Demine et al., 2014). Muscle glycogen is an important fuel during exercise due to its pronounced effects on substrate metabolism. To date, no study has explored whether a change in muscle glycogen content and thus substrate availability influences peak fat oxidation (PFO) and mitochondrial coupling control and efficiency (MCCE). The aim was therefore to investigate the influence of muscle glycogen content on PFO, the intensity that elicits PFO (Fatmax) and MCCE. It was hypothesised that PFO and Fatmax would increase in a state of low muscle glycogen availability, whereas MCCE was expected to be higher in a state of medium to high muscle glycogen. METHODS: Ten trained men (age: 26.1±3.0 years, BMI: 23.3±1.6 kg/m2, 𝑉̇O2peak: 4.72±0.35 L O2/min) participated in a crossover study involving two interventions each consisting of two test days. Day 1 consisted of anthropometrics, blood sampling, a muscle biopsy, and a graded exercise test to measure PFO, Fatmax and 𝑉̇O2peak using an automated online system (Quark CPET, COSMED, Rome, Italy), followed by a 2.5-3-hour glycogen depletion protocol. On the following day, a blood sample and a muscle biopsy were collected, and the graded exercise test was repeated. An isocaloric diet high or low in carbohydrate was consumed between the days to manipulate glycogen levels and constituted a high-carbohydrate (H-CHO) and low-carbohydrate (L-CHO) intervention. The alternative diet was repeated 7-14 days later. Muscle samples were analysed for muscle glycogen content, and MCCE was assessed in isolated mitochondria using high-resolution respirometry (Oxygraph-2k; Oroboros Instruments GmbH, Innsbruck, Austria) . A two-way mixed-model ANOVA was used to assess both within-intervention changes in PFO and Fatmax and between-intervention differences. Changes in muscle glycogen and MCCE were analysed by a one-way ANOVA. RESULTS: Compared to baseline, muscle glycogen content was reduced by 30.5 % and 69.3 % in the H-CHO and L-CHO intervention, respectively. PFO increased under conditions of low muscle glycogen availability and was lower in H-CHO when compared to baseline values. Fatmax was elevated only under low muscle glycogen availability. Muscle glycogen content did not influence MCCE. CONCLUSION: The study design successfully manipulated muscle glycogen content through dietary and exercise interventions. As hypothesised, muscle glycogen content influenced both PFO and Fatmax. However, contrary to the hypothesis, diet and exercise induced short-term changes in muscle glycogen content did not significantly influence MCCE.
Read CV Kristine LangeECSS Paris 2023: OP-PN23
INTRODUCTION: Military roles are physically and psychologically demanding; energy intake may not always match high energy expenditures and Servicewomen may be at risk of outcomes associated with the Female Athlete Triad (Triad) and Relative Energy Deficiency in Sport (REDs) models. Chronic low energy availability may decrease physical performance through indirect endocrine effects—associated with menstrual disturbances—or direct effects such as under-fuelling. Whether markers of the Triad or REDs, including menstrual disturbances, eating disorders, and low energy availability are associated with physical performance in Servicewomen is unknown. METHODS: All women aged under 45 years in the British Army were invited to complete a custom-designed questionnaire that asked about: demographics, job role, risk of disordered eating (Brief Eating Disorder in Athletes Questionnaire), risk of low energy availability (Low Energy Availability in Females Questionnaire), training (military and personal), menstrual function, and physical performance (scores on military physical performance tests: 2 km run; deadlift). Physical performance was scored using British Army scoring categories. Inferential statistics were performed with ordinal logistic regression to assess the association of 2 km run time and maximal effort deadlift strength with the predictor variables: menstrual function, risk of eating disorders, and risk of low energy availability, when controlling for demographic factors and time spent physical training. Odds ratios represent the likelihood of moving from faster to slower run times or lighter to heavier lifts. RESULTS: 1,341 women participated with 825 included following the exclusion of those pregnant or had not completed a military physical fitness test in the last 12 months. Menstrual disturbance (oligomenorrhoea/amenorrhoea vs eumenorrhea) (odds ratio [95% confidence intervals], 2 km run: 1.01 [0.62, 1.65], p = 0.962; deadlift: 0.86 [0.53, 1.40], p = 0.548), risk of an eating disorder (high vs low) (2 km run: 1.20 [0.79, 1.84], p = 0.392; deadlift: 1.01 [0.44, 1.68], p = 0.951), and risk of low energy availability (high vs low) (2 km time: 1.10 [0.83, 1.47], p = 0.496; deadlift strength: 1.33 [0.99, 1.78], p = 0.058) were not associated with run time or lift strength. Higher volumes of personal physical training (2 km run: 0.13 [0.08, 0.23], p < 0.001; deadlift: 4.46 [2.49, 8.08], p < 0.001) but not military physical training (2 km run: 0.71 [0.42, 1.21], p = 0.207; deadlift: 1.41 [0.81, 2.46], p = 0.218) (5 h·week-1 vs 0 h·week-1) were associated with better run time and lift strength. CONCLUSION: Military-specific physical performance was not associated with indicators of menstrual function, eating disorders, or low energy availability in Servicewomen. The pathophysiology of menstrual disturbances, eating disorders, and low energy availability in Servicewomen may be different to athletes and influenced by the multi-stressor environment.
Read CV Charlotte CoombsECSS Paris 2023: OP-PN23