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A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Advances in Metabolomics".

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 47135

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Dr. Vassilis Mougios

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Laboratory of Evaluation of Human Biological Performance, School of Physical Education and Sport Science, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece
Interests: exercise biochemistry and physiology; exercise metabolomics; sport nutrition
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Dear Colleagues,

Metabolomics is being increasingly appreciated as an integral part of systems biology. Possessing the advantage of affording a holistic view of metabolism, metabolomics has been used repeatedly over the past decade in the study of the effects of exercise, both acute and chronic, on human and animal metabolism. Thus, the field of exercise metabonomics has emerged, which can be defined as the large-scale, comprehensive study of the effects of exercise on the metabolome. The aim of this Special Issue is to advance this field by providing a forum for the presentation of research findings based on a metabolomics approach and related to the modulation of metabolism by different exercise parameters (such as type, intensity, duration, and whether it is acute or chronic), characteristics of the exercising organism (such as sex, age, nutritional state, training state, and the genome), and environmental factors (such as ambient temperature and hypoxia).

Prof. Dr. Vassilis Mougios
Guest Editor

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Keywords

exercise
metabolomics/metabonomics
physical activity

Published Papers (11 papers)

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Research

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17 pages, 8056 KiB

Open AccessArticle

An Untargeted Metabolomics Approach to Investigate the Metabolic Effect of Beetroot Juice Supplementation in Fencers—A Preliminary Study

by Lucyna Kozlowska, Olga Mizera and Anna Mroz

Metabolites 2020, 10(3), 100; https://doi.org/10.3390/metabo10030100 - 11 Mar 2020

Cited by 11 | Viewed by 2822

Abstract

This study aimed at assessment of the long-term (4 weeks) metabolic effect of a diet with and without beetroot juice supplementation in fencers using the untargeted metabolomics method with the UPLC Q-TOF/MS system to carry out an analysis of urine samples. Ten women and 10 men underwent the cardiovascular fitness VO_2max test at baseline—(B) and after two stages of implementation of the dietary recommendations—the first 4 weeks without beetroot juice (D) and the second with 26 g/d of freeze-dried beetroot juice supplementation (D&J). The urine samples were collected one hour after the VO_2max test at B and after D and D&J. The meal before the VO_2max test after D&J contained beetroot juice, whereas to the meal at B and after D maltodextrin was added. Changes in metabolites and VO_2max were significant only for comparison of D versus D&J. During D and D&J, there were no significant changes in the physical activity level, body mass, and body composition. We observed significant changes in tyrosine and tryptophan metabolism, mainly associated with such neurotransmitter’s metabolism as: Serotonin, noradrenaline, and adrenaline. Changes in signal intensity of bile acid, AICAR, and 4-Hydroxynonenal (peroxidation of polyunsaturated fatty acids product) were also observed. The obtained results indicate that long-term beetroot juice supplementation induces considerable changes in metabolism. Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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14 pages, 2903 KiB

Open AccessArticle

Metabolite Shifts Induced by Marathon Race Competition Differ between Athletes Based on Level of Fitness and Performance: A Substudy of the Enzy-MagIC Study

by Jana F. Schader, Mark Haid, Alexander Cecil, Julia Schoenfeld, Martin Halle, Arne Pfeufer, Cornelia Prehn, Jerzy Adamski, David C. Nieman and Johannes Scherr

Metabolites 2020, 10(3), 87; https://doi.org/10.3390/metabo10030087 - 01 Mar 2020

Cited by 17 | Viewed by 3357

Abstract

This study compared metabolite shifts induced by training for, participation in, and recovery from a marathon race competition among athletes divided into three groups based on fitness (relative maximum oxygen uptake (VO₂max)) and performance levels (net running time). Plasma samples from 76 male runners participating in the Munich Marathon were analyzed for metabolite shifts using a targeted metabolomics panel. For the entire cohort of runners, pronounced increases were measured immediately after the race for plasma concentrations of acylcarnitines (AC), the ratio (palmitoylcarnitine + stearoylcarnitine)/free carnitine that is used as a proxy for the activity of the mitochondrial enzyme carnitine palmitoyltransferase, and arginine-related metabolites, with decreases in most amino acids (AA) and phospholipids. Plasma levels of AA and phospholipids were strongly increased 24 and 72 h post-race. Post-race plasma concentrations of AC and arginine-related metabolites were higher in the low compared to top performers, indicating an accumulation of fatty acids and a reliance on protein catabolism to provide energy after the marathon event. This study showed that marathon race competition is associated with an extensive and prolonged perturbation in plasma metabolite concentrations with a strong AC signature that is greater in the slower, less aerobically fit runners. Furthermore, changes in the arginine-related metabolites were observed. Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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11 pages, 888 KiB

Open AccessArticle

Chronic Influence of Inspiratory Muscle Training at Different Intensities on the Serum Metabolome

by Camila A. Sakaguchi, David C. Nieman, Etore F. Signini, Raphael M. de Abreu, Claudio D. Silva, Patrícia Rehder-Santos, Maria G. A. Carosio, Roberta M. Maria, Carla C. Dato, Heloisa S. S. de Araújo, Tiago Venâncio, Antônio G. Ferreira and Aparecida M. Catai

Metabolites 2020, 10(2), 78; https://doi.org/10.3390/metabo10020078 - 21 Feb 2020

Cited by 2 | Viewed by 2246

Abstract

This study investigated the chronic effect of inspiratory muscle training (IMT) on the human serum metabolome in healthy male recreational cyclists. Using a randomized, parallel group design, twenty-eight participants were randomized to three IMT groups: low intensity (LI, n = 7); moderate intensity (MI, n = 10); and high intensity (HI, n = 11). The IMT was performed for 11 weeks. Another group of participants under the same conditions, who did not perform the IMT but participated in all procedures, was included as controls (CG, n = 6). Blood samples were collected one week before and after 11 weeks of IMT and analyzed for metabolite shifts using 1H NMR. Statistical analysis included a 4 (group) × 2 (time) repeated measures ANOVA using the general linear model (GLM), and multivariate principal component analysis (PCA). Untargeted metabolomics analysis of serum samples identified 22 metabolites, including amino acids, lipids, and tricarboxylic acid cycle intermediates. Metabolites shifts did not differ between groups, indicating that IMT at three intensity levels did not alter the serum metabolome relative to the control group. These results reveal novel insights into the metabolic effects of the IMT and are consistent with the results from other studies showing negligible chronic alterations in the serum metabolome in response to physical training. Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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19 pages, 2846 KiB

Open AccessArticle

Salivary Metabolome and Soccer Match: Challenges for Understanding Exercise induced Changes

by Erica Pitti, Greta Petrella, Sara Di Marino, Vincenzo Summa, Marco Perrone, Stefano D’Ottavio, Andrea Bernardini and Daniel Oscar Cicero

Metabolites 2019, 9(7), 141; https://doi.org/10.3390/metabo9070141 - 11 Jul 2019

Cited by 26 | Viewed by 4210

Abstract

Saliva samples of seventeen soccer players were analyzed by nuclear magnetic resonance before and after an official match. Two different ways of normalizing data are discussed, using total proteins and total metabolite concentrations. Changes in markers related to energy, hydration status, amino acids and other compounds were found. The limits and advantages of using saliva to define the systemic responses to exercise are examined, both in terms of data normalization and interpretation, and the time that the effect lasts in this biofluid, which is shorter to that commonly observed in blood. The heterogeneous nature and different timing of the exercise developed by players also plays an important role in the metabolic changes that can be measured. Our work focuses mainly on three different aspects: The effect that time sampling has on the observed effect, the type of normalization that is necessary to perform in order to cope with changes in water content, and the metabolic response that can be observed using saliva. Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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18 pages, 825 KiB

Open AccessArticle

High-Intensity Interval Training Decreases Resting Urinary Hypoxanthine Concentration in Young Active Men—A Metabolomic Approach

by Sina Kistner, Manuela J. Rist, Ralf Krüger, Maik Döring, Sascha Schlechtweg and Achim Bub

Metabolites 2019, 9(7), 137; https://doi.org/10.3390/metabo9070137 - 10 Jul 2019

Cited by 12 | Viewed by 5190

Abstract

High-intensity interval training (HIIT) is known to improve performance and skeletal muscle energy metabolism. However, whether the body’s adaptation to an exhausting short-term HIIT is reflected in the resting human metabolome has not been examined so far. Therefore, a randomized controlled intervention study was performed to investigate the effect of a ten-day HIIT on the resting urinary metabolome of young active men. Fasting spot urine was collected before (−1 day) and after (+1 day; +4 days) the training intervention and 65 urinary metabolites were identified by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Metabolite concentrations were normalized to urinary creatinine and subjected to univariate statistical analysis. One day after HIIT, no overall change in resting urinary metabolome, except a significant difference with decreasing means in urinary hypoxanthine concentration, was documented in the experimental group. As hypoxanthine is related to purine degradation, lower resting urinary hypoxanthine levels may indicate a training-induced adaptation in purine nucleotide metabolism. Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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19 pages, 2399 KiB

Open AccessArticle

Metabolic Perturbations from Step Reduction in Older Persons at Risk for Sarcopenia: Plasma Biomarkers of Abrupt Changes in Physical Activity

by Michelle Saoi, Alice Li, Chris McGlory, Tanner Stokes, Mark T. von Allmen, Stuart M. Phillips and Philip Britz-McKibbin

Metabolites 2019, 9(7), 134; https://doi.org/10.3390/metabo9070134 - 08 Jul 2019

Cited by 40 | Viewed by 5996

Abstract

Sarcopenia is the age-related loss of skeletal muscle mass, strength and function, which may be accelerated during periods of physical inactivity. Declines in skeletal muscle and functionality not only impacts mobility but also increases chronic disease risk, such as type 2 diabetes. The aim of this study was to measure adaptive metabolic responses to acute changes in habitual activity in a cohort of overweight, pre-diabetic older adults (age = 69 ± 4 years; BMI = 27 ± 4 kg/m², n = 17) when using non-targeted metabolite profiling by multisegment injection-capillary electrophoresis-mass spectrometry. Participants completed two weeks of step reduction (<1000 steps/day) followed by a two week recovery period, where fasting plasma samples were collected at three time intervals at baseline, after step reduction and following recovery. Two weeks of step reduction elicited increases in circulatory metabolites associated with a decline in muscle energy metabolism and protein degradation, including glutamine, carnitine and creatine (q < 0.05; effect size > 0.30), as well as methionine and deoxycarnitine (p < 0.05; effect size ≈ 0.20) as compared to baseline. Similarly, decreases in uremic toxins in plasma that promote muscle inflammation, indoxyl sulfate and hippuric acid, as well as oxoproline, a precursor used for intramuscular glutathione recycling, were also associated with physical inactivity (p < 0.05; effect size > 0.20). Our results indicate that older persons are susceptible to metabolic perturbations due to short-term step reduction that were not fully reversible with resumption of normal ambulatory activity over the same time period. These plasma biomarkers may enable early detection of inactivity-induced metabolic dysregulation in older persons at risk for sarcopenia not readily measured by current imaging techniques or muscle function tests, which is required for the design of therapeutic interventions to counter these deleterious changes in support of healthy ageing. Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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14 pages, 1882 KiB

Open AccessArticle

Interpretation of Multivariate Association Patterns between Multicollinear Physical Activity Accelerometry Data and Cardiometabolic Health in Children—A Tutorial

by Eivind Aadland, Lars Bo Andersen, Geir Kåre Resaland and Olav Martin Kvalheim

Metabolites 2019, 9(7), 129; https://doi.org/10.3390/metabo9070129 - 02 Jul 2019

Cited by 20 | Viewed by 3332

Abstract

Associations between multicollinear accelerometry-derived physical activity (PA) data and cardiometabolic health in children needs to be analyzed using an approach that can handle collinearity among the explanatory variables. The aim of this paper is to provide readers a tutorial overview of interpretation of multivariate pattern analysis models using PA accelerometry data that reveals the associations to cardiometabolic health. A total of 841 children (age 10.2 ± 0.3 years) provided valid data on accelerometry (ActiGraph GT3X+) and six indices of cardiometabolic health that were used to create a composite score. We used a high-resolution PA description including 23 intensity variables covering the intensity spectrum (from 0–99 to ≥10000 counts per minute), and multivariate pattern analysis to analyze data. We report different statistical measures of the multivariate associations between PA and cardiometabolic health and use decentile groups of PA as a basis for discussing the meaning and impact of multicollinearity. We show that for high-resolution accelerometry data; considering all explanatory variables is crucial to obtain a correct interpretation of associations to cardiometabolic health; which is otherwise strongly confounded by multicollinearity in the dataset. Thus; multivariate pattern analysis challenges the traditional interpretation of findings from linear regression models assuming independent explanatory variables Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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17 pages, 3352 KiB

Open AccessArticle

Comparison of the Serum Metabolic Fingerprint of Different Exercise Modes in Men with and without Metabolic Syndrome

by Aikaterina Siopi, Olga Deda, Vasiliki Manou, Ioannis Kosmidis, Despina Komninou, Nikolaos Raikos, Georgios A. Theodoridis and Vassilis Mougios

Metabolites 2019, 9(6), 116; https://doi.org/10.3390/metabo9060116 - 15 Jun 2019

Cited by 17 | Viewed by 3459

Abstract

Exercise plays a beneficial role in the treatment of metabolic syndrome (MetS). Metabolomics can provide new insights and facilitate the optimization of exercise prescription. This study aimed to investigate whether the response of the human serum metabolic fingerprint to exercise depends on exercise mode or the presence of MetS. Twenty-three sedentary men (nine with MetS and fourteen healthy) completed four trials: Resting, high-intensity interval exercise (HIIE), continuous moderate-intensity exercise (CME), and resistance exercise (RE). Blood samples were collected pre-exercise, immediately after exercise, and 1 h post-exercise for targeted metabolomic analysis in serum by liquid chromatography–mass spectrometry. Time exerted the strongest differentiating effect, followed by exercise mode. The largest changes from baseline were found in the immediate post-exercise samples. RE caused the strongest responses overall, followed by HIIE, while CME had minimal effect. Unlike previous results in urine, no valid model could separate the two groups in serum. Exercise exerted a beneficial effect on prominent serum biomarkers of metabolic risks, such as branched-chain amino acids, alanine, acetylcarnitine, choline, and betaine. These findings contribute to the ongoing research efforts to map the molecular responses to exercise and to optimize exercise guidelines for individuals at cardiometabolic risk. Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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20 pages, 3161 KiB

Open AccessArticle

Plasma Free Fatty Acids Metabolic Profile with LC-MS and Appetite-Related Hormones in South Asian and White European Men in Relation to Adiposity, Physical Activity and Cardiorespiratory Fitness: A Cross-Sectional Study

by Simone Benedetti, Naser F. Al-Tannak, Mansour Alzharani, Hannah J. Moir, David J. Stensel, Alice E. Thackray, Declan P. Naughton, Mehmet T. Dorak, Owen Spendiff, Natasha Hill, David G. Watson and Judith Allgrove

Metabolites 2019, 9(4), 71; https://doi.org/10.3390/metabo9040071 - 13 Apr 2019

Cited by 8 | Viewed by 4961

Abstract

South Asians have a greater cardiovascular disease (CVD) and type 2 diabetes (T2D) risk than white Europeans, but the mechanisms are poorly understood. This study examined ethnic differences in free fatty acids (FFAs) metabolic profile (assessed using liquid chromatography-mass spectrometry), appetite-related hormones and traditional CVD and T2D risk markers in blood samples collected from 16 South Asian and 16 white European men and explored associations with body composition, objectively-measured physical activity and cardiorespiratory fitness. South Asians exhibited higher concentrations of five FFAs (laurate, myristate, palmitate, linolenic, linoleate; p ≤ 0.040), lower acylated ghrelin (ES = 1.00, p = 0.008) and higher leptin (ES = 1.11, p = 0.004) than white Europeans; total peptide YY was similar between groups (p = 0.381). South Asians exhibited elevated fasting insulin, C-reactive protein, interleukin-6, triacylglycerol and ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C) and lower fasting HDL-C (all ES ≥ 0.74, p ≤ 0.053). Controlling for body fat percentage (assessed using air displacement plethysmography) attenuated these differences. Despite similar habitual moderate-to-vigorous physical activity (ES = 0.18, p = 0.675),

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O_2max was lower in South Asians (ES = 1.36, p = 0.001). Circulating FFAs in South Asians were positively correlated with body fat percentage (r² = 0.92), body mass (r² = 0.86) and AUC glucose (r² = 0.89) whereas in white Europeans FFAs were negatively correlated with total step counts (r² = 0.96). In conclusion, South Asians exhibited a different FFA profile, lower ghrelin, higher leptin, impaired CVD and T2D risk markers and lower cardiorespiratory fitness than white Europeans. Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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16 pages, 3364 KiB

Open AccessArticle

The Effect of Exercise Training on Myocardial and Skeletal Muscle Metabolism by MR Spectroscopy in Rats with Heart Failure

by Mingshu Shi, Øyvind Ellingsen, Tone Frost Bathen, Morten A. Høydal, Tomas Stølen and Morteza Esmaeili

Metabolites 2019, 9(3), 53; https://doi.org/10.3390/metabo9030053 - 19 Mar 2019

Cited by 7 | Viewed by 4312

Abstract

The metabolism and performance of myocardial and skeletal muscle are impaired in heart failure (HF) patients. Exercise training improves the performance and benefits the quality of life in HF patients. The purpose of the present study was to determine the metabolic profiles in myocardial and skeletal muscle in HF and exercise training using MRS, and thus to identify targets for clinical MRS in vivo. After surgically establishing HF in rats, we randomized the rats to exercise training programs of different intensities. After the final training session, rats were sacrificed and tissues from the myocardial and skeletal muscle were extracted. Magnetic resonance spectra were acquired from these extracts, and principal component and metabolic enrichment analysis were used to assess the differences in metabolic profiles. The results indicated that HF affected myocardial metabolism by changing multiple metabolites, whereas it had a limited effect on skeletal muscle metabolism. Moreover, exercise training mainly altered the metabolite distribution in skeletal muscle, indicating regulation of metabolic pathways of taurine and hypotaurine metabolism and carnitine synthesis. Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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Review

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15 pages, 1108 KiB

Open AccessReview

Metabolomics-Based Studies Assessing Exercise-Induced Alterations of the Human Metabolome: A Systematic Review

by Camila A. Sakaguchi, David C. Nieman, Etore F. Signini, Raphael M. Abreu and Aparecida M. Catai

Metabolites 2019, 9(8), 164; https://doi.org/10.3390/metabo9080164 - 09 Aug 2019

Cited by 79 | Viewed by 6319

Abstract

This systematic review provides a qualitative appraisal of 24 high-quality metabolomics-based studies published over the past decade exploring exercise-induced alterations of the human metabolome. Of these papers, 63% focused on acute metabolite changes following intense and prolonged exercise. The best studies utilized liquid chromatography mass spectrometry (LC-MS/MS) analytical platforms with large chemical standard libraries and strong, multivariate bioinformatics support. These studies reported large-fold changes in diverse lipid-related metabolites, with more than 100 increasing two-fold or greater within a few hours post-exercise. Metabolite shifts, even after strenuous exercise, typically return to near pre-exercise levels after one day of recovery. Few studies investigated metabolite changes following acute exercise bouts of shorter durations (< 60 min) and workload volumes. Plasma metabolite shifts in these types of studies are modest in comparison. More cross-sectional and exercise training studies are needed to improve scientific understanding of the human system’s response to varying, chronic exercise workloads. The findings derived from this review provide direction for future investigations focused on the body’s metabolome response to exercise. Full article

(This article belongs to the Special Issue Exercise Metabonomics)

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