An NMR-Based Approach to Identify Urinary Metabolites Associated with Acute Physical Exercise and Cardiorespiratory Fitness in Healthy Humans-Results of the KarMeN Study.
ABSTRACT: Knowledge on metabolites distinguishing the metabolic response to acute physical exercise between fit and less fit individuals could clarify mechanisms and metabolic pathways contributing to the beneficial adaptations to exercise. By analyzing data from the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study, we characterized the acute effects of a standardized exercise tolerance test on urinary metabolites of 255 healthy women and men. In a second step, we aimed to detect a urinary metabolite pattern associated with the cardiorespiratory fitness (CRF), which was determined by measuring the peak oxygen uptake (VO2peak) during incremental exercise. Spot urine samples were collected pre- and post-exercise and 47 urinary metabolites were identified by nuclear magnetic resonance (NMR) spectroscopy. While the univariate analysis of pre-to-post-exercise differences revealed significant alterations in 37 urinary metabolites, principal component analysis (PCA) did not show a clear separation of the pre- and post-exercise urine samples. Moreover, both bivariate correlation and multiple linear regression analyses revealed only weak relationships between the VO2peak and single urinary metabolites or urinary metabolic pattern, when adjusting for covariates like age, sex, menopausal status, and lean body mass (LBM). Taken as a whole, our results show that several urinary metabolites (e.g., lactate, pyruvate, alanine, and acetate) reflect acute exercise-induced alterations in the human metabolism. However, as neither pre- and post-exercise levels nor the fold changes of urinary metabolites substantially accounted for the variation of the covariate-adjusted VO2peak, our results furthermore indicate that the urinary metabolites identified in this study do not allow to draw conclusions on the individual's physical fitness status. Studies investigating the relationship between the human metabolome and functional variables like the CRF should adjust for confounders like age, sex, menopausal status, and LBM.
Project description:Type 2 diabetes mellitus (T2DM) is associated with a reduction in muscle quality. However, there is inadequate empirical evidence to determine whether changes in muscle quality following exercise are associated with improvement in cardiorespiratory fitness (CRF) in individuals with T2DM. The objective of this study was to investigate the association between change in muscle quality following a 9-month intervention of aerobic training (AT), resistance training (RT) or a combination of both (ATRT) and cardiorespiratory fitness (CRF) in individuals with T2DM.A total of 196 participants were randomly assigned to a control, AT, RT, or combined ATRT for a 9-months intervention. The exposure variable was change in muscle quality [(Post: leg muscle strength/leg muscle mass)-[(Pre: leg muscle strength/leg muscle mass)]. Dependent variables were change in CRF measures including absolute and relative VO2peak, and treadmill time to exhaustion (TTE) and estimated metabolic equivalent task (METs).Continuous change in muscle quality was independently associated with change in absolute (? = 0.015; p = 0.019) and relative (? = 0.200; p = 0.005) VO2peak, and TTE (? = 0.170; p = 0.043), but not with estimated METs (p > 0.05). A significant trend was observed across tertiles of change in muscle quality for changes in absolute (? = 0.050; p = 0.005) and relative (? = 0.624; p = 0.002) VO2peak following 9 months of exercise training. No such association was observed for change in TTE and estimated METs (p > 0.05).The results from this ancillary study suggest that change in muscle quality following exercise training is associated with a greater improvement in CRF in individuals with T2DM. Given the effect RT has on increasing muscle quality, especially as part of a recommended training program (ATRT), individuals with T2DM should incorporate RT into their AT regimens to optimize CRF improvement.Clinicaltrials.gov NCT00458133.
Project description:Physical exercise (PE) has been shown to improve brain function via multiple neurobiological mechanisms promoting neuroplasticity. Cognitive exercise (CE) combined with PE may show an even greater effect on cognitive function. Brain-derived neurotrophic factor (BDNF) is important for neuroplastic signaling, may reduce with increasing age, and is confounded by fitness. The source and physiological role of human peripheral blood BDNF in plasma (pBDNF) is thought to differ from that in serum (sBDNF), and it is not yet known how pBDNF and sBDNF respond to PE and CE. A training intervention study in healthy older adults investigated the effects of acute (35 min) and prolonged (12 weeks, 30 sessions) CE and PE, both alone and in combination, on pBDNF and sBDNF. Cross-sectional associations between baseline pBDNF, sBDNF and cardiorespiratory fitness (CRF) were also investigated. Participants (65-75 years) were randomly assigned to four groups and prescribed either CE plus 35 min of rest (n = 21, 52% female); PE [performed on a cycle ergometer at moderate intensity (65-75% of individual maximal heart rate)] plus 35 min of rest (n = 27, 56% female); CE plus PE (n = 24, 46% female), or PE plus CE (n = 25, 52% female). Groups were tested for CRF using a maximal treadmill ergometer test (VO2peak); BDNF levels (collected 48 h after CRF) during baseline, after first exercise (PE or CE) and after second exercise (PE, CE or rest); and cognitive ability pre and post 12-week training. At both pre and post, pBDNF increased after CE and PE (up to 222%), and rest (?67%), whereas sBDNF increased only after PE (up to 18%) and returned to baseline after rest. Acute but not prolonged PE increased both pBDNF and sBDNF. CE induced acute changes in pBDNF only. Baseline pBDNF was positively associated with baseline sBDNF (n = 93, r = 0.407, p < 0.001). No changes in CRF were found in any of the groups. Baseline CRF did not correlate with baseline BDNF. Even though baseline pBDNF and sBDNF were associated, patterns of changes in pBDNF and sBDNF in response to exercise were explicitly different. Further experimental scrutiny is needed to clarify the biological mechanisms of these results.
Project description:Both indole-3-carbinol and dietary lignans have beneficial effects on estrogen metabolism and breast cancer risk. There is no published literature on the effects of a combination product. This study was designed to investigate the impact of a combination product on estrogen metabolism. The major trial objective was to determine whether a breast health supplement containing indole-3-carbinol and hydroxymatairesinol lignan would alter estrogen metabolism to favour C-2 hydroxylation and reduce C-16 hydroxylation. Higher concentrations of C-2 metabolites and lower concentrations of C-16 metabolites may reduce breast cancer risk and risk for other hormonally-related cancers.Forty-seven pre-menopausal and forty-nine post-menopausal women were recruited for this study, and were divided by random allocation into treatment and placebo group. The treatment supplement contained HMR lignan, indole-3-carbinol, calcium glucarate, milk thistle, Schisandra chinesis and stinging nettle, and each woman consumed either treatment or placebo for 28 days. At day 0 and day 28, blood samples were analysed for serum enterolactone concentrations, and first morning random urine samples were assessed for estrogen metabolites. Repeated measures ANOVA statistical testing was performed.In pre-menopausal women, treatment supplementation resulted in a significant increase (P < 0.05) in urinary 2-OHE concentrations and in the 2:16α-OHE ratio. In post-menopausal women, treatment supplementation resulted in a significant increase in urinary 2-OHE concentrations. In pre- and post-menopausal women combined, treatment supplementation produced a significant increase in urinary 2-OHE concentration and a trend (P = 0.074) toward an increased 2:16α-OHE ratio. There were no significant increases in serum enterolactone concentrations in the treatment or placebo groups.Supplementation with a mixture of indole-3-carbinol and HMR lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers. Further studies with higher numbers of subjects are indicated.
Project description:Background:Although numerous studies have reported the effect of inspiratory muscle training for improving exercise performance, the outcome of whether exercise performance is improved by inspiratory muscle training is controversial. Therefore, this study investigated the influence of inspiratory muscle-loaded exercise training (IMLET) on peak oxygen uptake (VO2peak), respiratory responses, and exercise performance under normoxic (N) and hypoxic (H) exercise conditions. We hypothesised that IMLET enhances respiratory muscle strength and improves respiratory response, thereby improving VO2peak and work capacity under H condition. Methods:Sixteen university track runners (13 men and 3 women) were randomly assigned to the IMLET (n?=?8) or exercise training (ET) group (n?=?8). All subjects underwent 4?weeks of 20-min 60% VO2peak cycling exercise training, thrice per week. IMLET loaded 50% of maximal inspiratory pressure during exercise. At pre- and post-training periods, subjects performed exhaustive incremental cycling under normoxic (N; 20.9?±?0%) and hypoxic (H; 15.0?±?0.1%) conditions. Results:Although maximal inspiratory pressure (PImax) significantly increased after training in both groups, the extent of PImax increase was significantly higher in the IMLET group (from 102?±?20 to 145?±?26 cmH2O in IMLET; from 111?±?23 to 127?±?23 cmH2O in ET; P?<?0.05). In both groups, VO2peak and maximal work load (Wmax) similarly increased both under N and H conditions after training (P?<?0.05). Further, the extent of Wmax decrease under H condition was lower in the IMLET group at post-training test than at pre-training (from -?14.7?±?2.2% to -?12.5?±?1.7%; P?<?0.05). Maximal minute ventilation in both N and H conditions increased after training than in the pre-training period. Conclusions:Our IMLET enhanced the respiratory muscle strength, and the decrease in work capacity under hypoxia was reduced regardless of the increase in VO2peak.
Project description:The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO2peak), maximal oxygen consumption normalized for body weight (VO2peak/kg), and oxygen consumption at the anaerobic threshold (VO2@AT). In women, 1 mL/min higher VO2peak, VO2peak/kg, and VO2@AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF.
Project description:We examined hypertrophic outcomes of weekly graded whey protein dosing (GWP) vs. whey protein (WP) or maltodextrin (MALTO) dosed once daily during 6 weeks of high-volume resistance training (RT). College-aged resistance-trained males (training age = 5 ± 3 years; mean ± SD) performed 6 weeks of RT wherein frequency was 3 d/week and each session involved 2 upper- and 2 lower-body exercises (10 repetitions/set). Volume increased from 10 sets/exercise (week 1) to 32 sets/exercise (week 6), which is the highest volume investigated in this timeframe. Participants were assigned to WP (25 g/d; <i>n</i> = 10), MALTO (30 g/d; <i>n</i> = 10), or GWP (25-150 g/d from weeks 1-6; <i>n</i> = 11), and supplementation occurred throughout training. Dual-energy x-ray absorptiometry (DXA), vastus lateralis (VL), and biceps brachii ultrasounds for muscle thicknesses, and bioelectrical impedance spectroscopy (BIS) were performed prior to training (PRE) and after weeks 3 (MID) and 6 (POST). VL biopsies were also collected for immunohistochemical staining. The GWP group experienced the greatest PRE to POST reduction in DXA fat mass (FM) (-1.00 kg, <i>p</i> < 0.05), and a robust increase in DXA fat- and bone-free mass [termed lean body mass (LBM) throughout] (+2.93 kg, <i>p</i> < 0.05). However, the MALTO group also experienced a PRE to POST increase in DXA LBM (+2.35 kg, <i>p</i> < 0.05), and the GWP and MALTO groups experienced similar PRE to POST increases in type II muscle fiber cross-sectional area (~+300 ?m<sup>2</sup>). When examining the effects of training on LBM increases (?LBM) in all participants combined, PRE to MID (+1.34 kg, <i>p</i> < 0.001) and MID to POST (+0.85 kg, <i>p</i> < 0.001) increases were observed. However, when adjusting ?LBM for extracellular water (ECW) changes, intending to remove the confounder of edema, a significant increase was observed from PRE to MID (+1.18 kg, <i>p</i> < 0.001) but not MID to POST (+0.25 kg; <i>p</i> = 0.131). Based upon DXA data, GWP supplementation may be a viable strategy to improve body composition during high-volume RT. However, large LBM increases observed in the MALTO group preclude us from suggesting that GWP supplementation is clearly superior in facilitating skeletal muscle hypertrophy. With regard to the implemented RT program, ECW-corrected ?LBM gains were largely dampened, but still positive, in resistance-trained participants when RT exceeded ~20 sets/exercise/wk.
Project description:In South Asians, a unique obesity phenotype of high abdominal fat is associated with increased cardiovascular risk. Low cardiorespiratory fitness (CRF) is associated with abdominal fat and an increased risk of cardiovascular disease. The purpose of this paper is to determine whether CRF as assessed by VO2 peak, in post-menopausal South Asian women, was associated with body fat distribution and abdominal fat. Physically inactive post-menopausal South Asian women (n = 55) from the Greater Vancouver area were recruited and assessed from January to August 2014. At baseline, VO2 peak was measured with the Bruce Protocol, abdominal fat with CT imaging, and body composition with dual energy X-ray absorptiometry. ANOVA was used to assess differences in subcutaneous abdominal adipose tissue (SAAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) between tertiles of CRF. Bivariate correlation and multiple linear regression analyses explored the association between VO2 peak with SAAT, VAT, TAAT and body composition. Models were further adjusted for body fat and body mass index (BMI). Compared to women in the lowest tertile of VO2 peak (13.8-21.8 mL/kg/min), women in the highest tertile (25.0-27.7 mL/kg/min) had significantly lower waist circumference, BMI, total body fat, body fat percentage, lean mass, SAAT, VAT and TAAT (p < 0.05). We found VO2 peak to be negatively associated with SAAT, VAT and TAAT, independent of age and body fatness but not independent of BMI. Further research is necessary to assess whether exercise and therefore improvements in CRF would alter SAAT, VAT and TAAT in post-menopausal South Asian women.
Project description:Aerobic exercise has been associated with reduced burden of brain and cognitive changes related to Alzheimer's disease (AD). However, it is unknown whether exercise training in asymptomatic individuals harboring risk for AD improves outcomes associated with AD. We investigated the effect of 26 weeks of supervised aerobic treadmill exercise training on brain glucose metabolism and cognition among 23 late-middle-aged adults from a cohort enriched with familial and genetic risk of AD. They were randomized to Usual Physical Activity (PA) or Enhanced PA conditions. Usual PA received instruction about maintaining an active lifestyle. Enhanced PA completed a progressive exercise training program consisting of 3 sessions of treadmill walking per week for 26 weeks. By week seven, participants exercised at 70- 80% heart rate reserve for 50 minutes per session to achieve 150 minutes of moderate intensity activity per week in accordance with public health guidelines. Before and after the intervention, participants completed a graded treadmill test to assess VO2peak as a measure of cardiorespiratory fitness (CRF), wore an accelerometer to measure free-living PA, underwent 18F-fluorodeoxyglucose positron emission tomography imaging to assess brain glucose metabolism, and a neuropsychological battery to assess episodic memory and executive function. VO2peak increased, sedentary behavior decreased, and moderate-to-vigorous PA increased significantly in the Enhanced PA group as compared to Usual PA. Glucose metabolism in the posterior cingulate cortex (PCC) did not change significantly in Enhanced PA relative to Usual PA. However, change in PCC glucose metabolism correlated positively with change in VO2peak. Executive function, but not episodic memory, was significantly improved after Enhanced PA relative to Usual PA. Improvement in executive function correlated with increased VO2peak. Favorable CRF adaptation after 26 weeks of aerobic exercise training was associated with improvements in PCC glucose metabolism and executive function, important markers of AD.
Project description:BACKGROUND: To evaluate the metabolic changes in urinary steroids in pre- and post-menopausal women and men with papillary thyroid carcinoma (PTC). METHODS: Quantitative steroid profiling combined with gas chromatography-mass spectrometry was used to measure the urinary concentrations of 84 steroids in both pre- (n = 21, age: 36.95 ± 7.19 yr) and post-menopausal female (n = 19, age: 52.79 ± 7.66 yr), and male (n = 16, age: 41.88 ± 8.48 yr) patients with PTC. After comparing the quantitative data of the patients with their corresponding controls (pre-menopause women: n = 24, age: 33.21 ± 10.48 yr, post-menopause women: n = 16, age: 49.67 ± 8.94 yr, male: n = 20, age: 42.75 ± 4.22 yr), the levels of steroids in the patients were normalized to the mean concentration of the controls to exclude gender and menopausal variations. RESULTS: Many urinary steroids were up-regulated in all PTC patients compared to the controls. Among them, the levels of three active androgens, androstenedione, androstenediol and 16?-hydroxy DHEA, were significantly higher in the pre-menopausal women and men with PTC. The corticoid levels were increased slightly in the PTC men, while progestins were not altered in the post-menopausal PTC women. Estrogens were up-regulated in all PTC patients but 2-hydroxyestrone and 2-hydroxy-17?-estradiol were remarkably changed in both pre-menopausal women and men with PTC. For both menopausal and gender differences, the 2-hydroxylation, 4-hydroxylation, 2-methoxylation, and 4-methoxylation of estrogens and 16?-hydroxylation of DHEA were differentiated between pre- and post-menopausal PTC women (P < 0.001). In particular, the metabolic ratio of 2-hydroxyestrone to 2-hydroxy-17?-estradiol, which could reveal the enzyme activity of 17?-hydroxysteroid dehydrogenase, showed gender differences in PTC patients (P < 1 × 10-7). CONCLUSIONS: These results are expected be helpful for better understanding the pathogenic differences in PTC according to gender and menopausal conditions.
Project description:Background:Although sugars and sugar derivatives are an important class of metabolites involved in many physiologic processes, there is limited knowledge on their occurrence and pattern in biofluids. Objective:Our aim was to obtain a comprehensive urinary sugar profile of healthy participants and to demonstrate the wide applicability and usefulness of this sugar profiling approach for nutritional as well as clinical studies. Design:In the cross-sectional KarMeN study, the 24-h urine samples of 301 healthy participants on an unrestricted diet, assessed via a 24-h recall, were analyzed by a newly developed semitargeted gas chromatography-mass spectrometry (GC-MS) profiling method that enables the detection of known and unknown sugar compounds. Statistical analyses were performed with respect to associations of sex and diet with the urinary sugar profile. Results:In total, 40 known and 15 unknown sugar compounds were detected in human urine, ranging from mono- and disaccharides, polyols, and sugar acids to currently unknown sugar-like compounds. A number of rarely analyzed sugars were found in urine samples. Maltose was found in statistically higher concentrations in the urine of women compared with men and was also associated with menopausal status. Further, a number of individual sugar compounds associated with the consumption of specific foods, such as avocado, or food groups, such as alcoholic beverages and dairy products, were identified. Conclusions:We here provide data on the complex nature of the sugar profile in human urine, of which some compounds may have the potential to serve as dietary markers or early disease biomarkers. Thus, comprehensive urinary sugar profiling not only has the potential to increase our knowledge of host sugar metabolism, but can also reveal new dietary markers after consumption of individual food items, and may lead to the identification of early disease biomarkers in the future. The KarMeN study was registered at drks.de as DRKS00004890.