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Metabolism oscillates between catabolic and anabolic states depending on food intake, exercise, or stresses that change a multitude of metabolic pathways simultaneously. We present the HuMet Repository for exploring dynamic metabolic responses to oral glucose/lipid loads, mixed meals, 36-h fasting, exercise, and cold stress in healthy subjects. Metabolomics data from blood, urine, and breath of 15 young, healthy men at up to 56 time points are integrated and embedded within an interactive web application, enabling researchers with and without computational expertise to search, visualize, analyze, and contextualize the dynamic metabolite profiles of 2,656 metabolites acquired on multiple platforms. With examples, we demonstrate the utility of the resource for research into the dynamics of human metabolism, highlighting differences and similarities in systemic metabolic responses across challenges and the complementarity of metabolomics platforms. The repository, providing a reference for healthy metabolite changes to six standardized physiological challenges, is freely accessible through a web portal., Competing Interests: Declaration of interests R.P.M. reports previously working for Metabolon, Inc., and being employed by, and having ownership interest in, Owlstone Medical, Inc. M.A. and G.K. are co-inventors (through Duke University/Helmholtz Zentrum München) on patents regarding applications of metabolomics in diseases of the central nervous system and hold equity in Chymia, LLC, and intellectual property in PsyProtix and Atai that are exploring the potential for therapeutic applications targeting mitochondrial metabolism in depression., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Dietary strategies to improve arachidonic acid:eicosapentaenoic acid (AA:EPA) ratios are of interest due to potential reductions in inflammation and oxidative stress following exercise. The aim of this study was to investigate the impact of a novel dietary intervention, that is, the ingestion of 30 g of dark chocolate, on blood lipid profiles and gut microbiota composition in elite male soccer players., Methods: Professional male soccer players were randomly assigned to the experimental group (DC) provided with 30 g of dark chocolate or to the control group (WC), provided with 30 g of white chocolate, for 30 days. Before and after intervention, blood, fecal sample, and anthropometry data were collected. For each outcome, two-way repeated-measure analysis of variance was used to identify differences between baseline and endpoint (Week 4), considering treatment (dark chocolate, white chocolate) as intersubjects' factors. Metagenomic analysis was performed following the general guidelines, which relies on the bioBakery computational environment., Results: DC group showed increased plasma polyphenols (from 154.7 ± 18.6 μg gallic acid equivalents/ml to 185.11 ± 57.6 μg gallic acid equivalents/ml, Δ pre vs. post = +30.41 ± 21.50) and significant improvements in lipid profiles: total cholesterol (Δ -32.47 ± 17.18 mg/dl DC vs. Δ -2.84 ± 6.25 mg/dl WC, Time × Treatment interaction p < .001), triglycerides (Δ -6.32 ± 4.96 mg/dl DC vs. Δ -0.42 ± 6.47 mg/dl WC, Time × Treatment interaction p < .001), low-density lipoprotein (Δ -18.42 ± 17.13 mg/dl vs. Δ -2.05 ± 5.19 mg/dl WC, Time × Treatment interaction p < .001), AA/EPA ratio (Δ -5.26 ± 2.35; -54.1% DC vs. Δ -0.47 ± 0.73, -6.41% WC, Time × Treatment interaction p < .001) compared with WC group. In addition, 4 weeks of intervention showed a significant increase in high-density lipoprotein concentration in DC group (Δ + 3.26 ± 4.49 mg/dl DC vs. Δ -0.79 ± 5.12 mg/dl WC). Microbial communities in the DC group maintained a slightly higher microbial stability over time (exhibiting lower within-subject community dissimilarity)., Conclusion: Ingesting 30 g of dark chocolate over 4 weeks positively improved AA:EPA ratio and maintained gut microbial stability. Dark chocolate ingestion represents an effective nutritional strategy to improve blood lipid profiles in professional soccer players. What Are the Findings? Ingesting 30 g of dark chocolate for 4 weeks positively influences blood lipid AA: EPA ratio while maintaining gut microbial stability. What This Study Adds? Dietary intake of specific foods such as dark chocolate represents an alternative strategy to support the health and recovery of elite soccer players. What Impact Might This Have on Clinical Practice in the Future? From a clinical and translational perspective, dark chocolate ingestion positively modulates favorable blood lipid profiles and polyunsaturated fatty acid metabolism while maintaining gut microbial stability. Dark chocolate ingestion may be considered as an effective nutritional strategy in elite sport environments during periods of high-intensity training and congested competitions. Further research is required to determine functional outcomes associated with the observed improvements in blood lipid profiles.

Context: How pre-exercise meal composition influences metabolic and health responses to exercise later in the day is currently unclear., Objective: Examine the effects of substituting carbohydrate for protein at lunch on subsequent exercise metabolism, appetite, and energy intake., Methods: Twelve healthy males completed three trials in randomized, counterbalanced order. Following a standardized breakfast (779 ± 66 kcal; ∼08:15), participants consumed a lunch (1186 ± 140 kcal; ∼13:15) containing either 0.2 g·kg-1 carbohydrate and ∼2 g·kg-1 protein (LO-CARB), 2 g·kg-1 carbohydrate and ∼0.4 g·kg-1 protein (HI-CARB), or fasted (FAST). Participants later cycled at ∼60% V̇O2peak for 1 h (∼16:15) and post-exercise ad-libitum energy intake was measured (∼18:30). Substrate oxidation, subjective appetite, and plasma concentrations of glucose, insulin, non-esterified fatty acids (NEFA), peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and acylated ghrelin (AG) were measured for 5 h post-lunch., Results: Fat oxidation was greater during FAST (+11.66 ± 6.63 g) and LO-CARB (+8.00 ± 3.83 g) than HI-CARB (p < 0.001), with FAST greater than LO-CARB (+3.67 ± 5.07 g; p < 0.05). NEFA were lowest in HI-CARB and highest in FAST, with insulin demonstrating the inverse response (all p < 0.01). PYY and GLP-1 demonstrated a stepwise pattern, with LO-CARB greatest and FAST lowest (all p < 0.01). AG was lower during HI-CARB and LO-CARB versus FAST (p < 0.01). Energy intake in LO-CARB was lower than FAST (-383 ± 233 kcal; p < 0.001) and HI-CARB (-313 ± 284 kcal; p < 0.001)., Conclusion: Substituting carbohydrate for protein in a pre-exercise lunch increased fat oxidation, suppressed subjective and hormonal appetite, and reduced post-exercise energy intake., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Frontotemporal dementia (FTD) is a neurodegenerative disorder that affects the frontal and temporal lobes of the brain, primarily in individuals under 65 years of age, and is the second most common form of dementia worldwide. There is no cure for FTD and current treatments offer limited symptomatic relief. Regular physical activity exhibits cognitive and neuroprotective benefits in healthy individuals and in various neurodegenerative diseases, such as Alzheimer's disease, but few studies have examined its efficacy in FTD. Accordingly, we investigated the impact of voluntary exercise training (VET) on the metabolic and behavioral characteristics of the rTg4510 transgenic mouse model of familial FTD. We show that regardless of genotype, VET increased energy expenditure, decreased sleep duration, and improved long-term memory in rTg4510 mice and WT littermates. Moreover, VET appeared to improve hyperactivity, a common feature of FTD, in rTg4510 mice. Although further work is required, these findings provide important insights into the potential benefits of physical activity in FTD., Competing Interests: Declaration of Competing Interest M.A.F. is a shareholder and scientific advisor for N-Gene Pharmaceuticals. M.A.F. is the founder and shareholder of Celesta Therapeutics., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

The impacts of carbohydrate (CHO) availability on time to task failure (TTF) and physiological responses to exercise at the maximal lactate steady state (MLSS) have not been studied. Ten participants (3 females, 7 males) completed this double-blinded, placebo-controlled study that involved a ramp incremental test, MLSS determination, and four TTF trials at MLSS, all performed on a cycle ergometer. With the use of a combination of nutritional (CHO, 7 g/kg, and placebo, PLA, 0 g/kg drinks) and exercise interventions [no exercise (REST) and glycogen-reducing exercise (EX)], the four conditions were expected to differ in preexercise CHO availability (REST CHO > REST PLA > EX CHO > EX PLA ). TTF at MLSS was not improved by CHO loading, as REST CHO (57.1 [16.6] min) and REST PLA (57.1 [15.6] min) were not different ( P = 1.00); however, TTF was ∼50% shorter in EX conditions compared with REST conditions on average ( P < 0.05), with EX CHO (39.1 [9.2] min) ∼90% longer than EX PLA (20.6 [6.9] min; P < 0.001). There were effects of condition for all perceptual and cardiometabolic variables when compared at isotime ( P < 0.05) and task failure (TF; P < 0.05), except for ventilation, perceptual responses, and neuromuscular function measures, which were not different at TF ( P > 0.05). Blood lactate concentration was stable in all conditions for participants who completed 30 min of exercise. These findings indicate that TTF at MLSS is not enhanced by preexercise CHO supplementation, but recent intense exercise decreases TTF at MLSS even with CHO supplementation. Extreme fluctuations in diet and strenuous exercise that reduce CHO availability should be avoided before MLSS determination. NEW & NOTEWORTHY Carbohydrate (CHO) loading did not increase participants' ability to cycle at their maximal lactate steady state (MLSS); however, performing a glycogen depletion task the evening before cycling at MLSS reduced the time to task failure, even when paired with a high dose of CHO. These diet and exercise interventions influenced blood lactate concentration ([BLa]) but not the stability of [BLa]. Activities that reduce CHO availability should be avoided before MLSS determination.

During aerobic exercise, women oxidize significantly more lipids and less carbohydrates than men. This sexual dimorphism in substrate metabolism has been attributed, in part, to the observed differences in epinephrine and glucagon levels between men and women during exercise. To identify the underpinning candidate physiological mechanisms for these sex differences, we developed a sex-specific multi-scale mathematical model that relates cellular metabolism in the organs to whole-body responses during exercise. We conducted simulations to test the hypothesis that sex differences in the exercise-induced changes to epinephrine and glucagon would result in the sexual dimorphism of hepatic metabolic flux rates via the glucagon-to-insulin ratio (GIR). Indeed, model simulations indicate that the shift towards lipid metabolism in the female model is primarily driven by the liver. The female model liver exhibits resistance to GIR-mediated glycogenolysis, which helps maintain hepatic glycogen levels. This decreases arterial glucose levels and promotes the oxidation of free fatty acids. Furthermore, in the female model, skeletal muscle relies on plasma free fatty acids as the primary fuel source, rather than intramyocellular lipids, whereas the opposite holds true for the male model., (© 2024. The Author(s), under exclusive licence to Society for Mathematical Biology.)

The human gut microbiota can be compared to a fingerprint due to its uniqueness, hosting trillions of living organisms. Taking a sport-centric perspective, the gut microbiota might represent a physiological system that relates to health aspects as well as individualized performance in athletes. The athletes' physiology has adapted to their exceptional lifestyle over the years, including the diversity and taxonomy of the microbiota. The gut microbiota is influenced by several physiological parameters and requires a highly individual and complex approach to unravel the linkage between performance and the microbial community. This approach has been taken in this review, highlighting the functions that the microbial community performs in sports, naming gut-centered targets, and aiming for both a healthy and sustainable athlete and performance development. With this article, we try to consider whether initiating a microbiota analysis is practicable and could add value in elite sport, and what possibilities it holds when influenced through a variety of interventions. The aim is to support enabling a well-rounded and sustainable athlete and establish a new methodology in elite sport.

Objective: Phenylcapsaicin (PC) is a new capsaicin analog which has exhibited a higher bioavailability. This sudy assessed the effects of a low dose (LD) of 0.625 mg and a high dose (HD) of 2.5 mg of PC on aerobic capacity, substrate oxidation, energy metabolism and exercise physiological variables in young males. Materials and methods: Seventeen active males (age = 24.7 ± 6.0 years) enrolled to this randomized, triple-blinded, placebo-controlled, crossover trial. Participants attended the laboratory on 4 sessions separated by 72-96 h. A submaximal exercise test [to determine maximal fat oxidation (MFO) and the intensity at MFO (FATmax)] followed by a maximal incremental test (to determine VO2 max ) were performed in a preliminary session. The subsequent sessions only differed in the supplement ingested [LD, HD or placebo (PLA)] and consisted of a steady-state test (60 min at FATmax) followed by a maximal incremental test. Energy metabolism, substrate oxidation, heart rate, general (gRPE) and quadriceps (RPEquad) rate of perceived exertion, skin temperature and thermal perception were tested. Results: Clavicle thermal perception was lower in HD compared to PLA and LD ( p = 0.04) across time. HD reduced maximum heart rate in comparison to PLA and LD ( p = 0.03). LD reported higher general RPE (RPEg) values during the steady-state test compared to PLA and HD across time ( p = 0.02). HD and LD elicited higher peak of fat oxidation during the steady-state test compared with PLA ( p = 0.05). Intra-test analyses revealed significant differences for fat oxidation (FATox) in favor of HD and LD compared to PLA ( p = 0.002 and 0.002, respectively), and for carbohydrate oxidation (CHOox) ( p = 0.05) and respiratory exchange ratio (RER) ( p = 0.03) for PLA. In the incremental test, only general RPE at 60% of the maximal intensity (W) differed favoring HD ( p ≤ 0.05). Conclusion: Therefore, PC may contribute to increase aerobic capacity through the improvement of fat oxidation, maximum heart rate and perceptual responses during exercise., Competing Interests: PJ-M, DJ, JM-O, and CA-F are scientific advisors of a sports supplement brand (Life Pro Nutrition). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiménez-Martínez, Alix-Fages, Janicijevic, Miras-Moreno, Chacón-Ventura, Martín-Olmedo, De La Cruz-Márquez, Osuna-Prieto, Jurado-Fasoli, Amaro-Gahete, García-Ramos and Colado.)

Introduction: Physiological limits imposed by vest-borne loads must be defined for optimal performance monitoring of the modern dismounted warfighter., Purpose: To evaluate how weighted vests affect locomotion economy and relative cardiometabolic strain during military load carriage while identifying key physiological predictors of exhaustion limits., Methods: Fifteen US Army soldiers (4 women, 11 men; age, 26 ± 8 years; height, 173 ± 10 cm; body mass (BM), 79 ± 16 kg) performed four incremental walking tests with different vest loads (0, 22, 44, or 66% BM). We examined the effects of vest-borne loading on peak walking speed, the physiological costs of transport, and relative work intensity. We then sought to determine which of the cardiometabolic indicators (oxygen uptake, heart rate, respiration rate) was most predictive of task failure., Results: Peak walking speed significantly decreased with successively heavier vest loads (p < 0.01). Physiological costs per kilometer walked were significantly higher with added vest loads for each measure (p < 0.05). Relative oxygen uptake and heart rate were significantly higher during the loaded trials than the 0% BM trial (p < 0.01) yet not different from one another (p > 0.07). Conversely, respiration rate was significantly higher with the heavier load in every comparison (p < 0.01). Probability modeling revealed heart rate as the best predictor of task failure (marginal R 2 , 0.587, conditional R 2 , 0.791)., Conclusion: Heavy vest-borne loads cause exceptional losses in performance capabilities and increased physiological strain during walking. Heart rate provides a useful non-invasive indicator of relative intensity and task failure during military load carriage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Purpose: To investigate the response of a targeted fraction of (168 metabolites) of the resting serum metabolome to 9 sessions of sprint interval training (SIT)., Methods: Thirty-four recreationally active males provided resting blood samples before (baseline) and 48-72 h after (post) a short-term (9 sessions) cycle ergometer-based SIT intervention. A targeted analysis of 168 metabolites was performed on serum using liquid chromatography mass spectrometry (LC-MS). 160 distinct metabolites were identified and combined with 4 calculated metabolite sums and 3 calculated metabolite ratios creating a panel of 167 individual factors. Data were analysed using principal component analysis and univariate testing of all factors classified into 5 metabolite subgroups., Results: SIT improved anaerobic capacity measured by average power output during a Wingate test (p < 0.01; mean difference = 38 W, 95% confidence interval [26, 51]) and aerobic capacity measured by average power output in a 20 min cycling test (p < 0.01; 17 W [12, 23]). Limited separation was discernible in the targeted serum metabolome between baseline and post-intervention when projected on the first and second principal component(s). However, univariate testing identified 11 fatty acids that had lower concentrations (false discovery rate < 0.05) in post-intervention samples., Conclusions: These findings demonstrate that this short-term SIT intervention had limited effect on the serum metabolome at rest, but a subfraction of fatty acids are potentially sensitive to short-term exercise training., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Research should equitably reflect responses in men and women. Including women in research, however, necessitates an understanding of the ovarian hormones and menstrual phase variations in both cellular and systems physiology. This review outlines recent advances in the multiplicity of ovarian hormone molecular signaling that elucidates the mechanisms for menstrual phase variability in exercise metabolism. The prominent endogenous estrogen, 17-β-estradiol (E2), molecular structure is bioactive in stabilizing plasma membranes and quenching free radicals and both E2 and progesterone (P4) promote the expression of antioxidant enzymes attenuating exercise-induced muscle damage in the late follicular (LF) and mid-luteal (ML) phases. E2 and P4 bind nuclear hormone receptors and membrane-bound receptors to regulate gene expression directly or indirectly, which importantly includes cross-regulated expression of their own receptors. Activation of membrane-bound receptors also regulates kinases causing rapid cellular responses. Careful analysis of these signaling pathways explains menstrual phase-specific differences. Namely, E2-promoted plasma glucose uptake during exercise, via GLUT4 expression and kinases, is nullified by E2-dominant suppression of gluconeogenic gene expression in LF and ML phases, ameliorated by carbohydrate ingestion. E2 signaling maximizes fat oxidation capacity in LF and ML phases, pending low-moderate exercise intensities, restricted nutrient availability, and high E2:P4 ratios. P4 increases protein catabolism during the luteal phase by indeterminate mechanisms. Satellite cell function supported by E2-targeted gene expression is countered by P4, explaining greater muscle strengthening from follicular phase-based training. In totality, this integrative review provides causative effects, supported by meta-analyses for quantitative actuality, highlighting research opportunities and evidence-based relevance for female athletes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The aim of this study was to summarize evidence on energy metabolism through peak fat oxidation (PFO) and maximum fat oxidation (Fat max ), as well as to analyze the protocols used in people with spinal cord injury (SCI) and to examine the main factors related to fat oxidation ability (i.e., age, sex, level of physical activity, and level and degree of injury)., Methods: Studies to determine PFO and Fat max using indirect calorimetry with an arm exercise protocol for SCI patients were included after a systematic search. Other endpoints included study design, sample size, control group, demographic data, level of injury, physical condition, protocol, outcomes measured, and statistical findings., Results: Eight studies (n = 560) were included. The mean value of VO 2peak was 1.86 L∙min -1 (range 0.75-2.60 L∙min -1 ) (lowest value in the tetraplegic subjects). The PFO ranged between 0.06 and 0.30 g∙min -1 (lowest rates: the non-trained subjects with cervical SCI; highest: the tetraplegic subjects). Two types of exercise protocol were found: arm cycle ergometer, and wheelchair propulsion with a computerized ergometer. Five studies used an incremental protocol (2-3 min/stage, different load increments); the rest performed tests of 20 min/stage at three intensities., Conclusion: There are few existing studies measuring fat oxidation in SCI, many of which used small and heterogeneous samples. PFO was lower in SCI subjects when compared with non-injured people performing lower-limb exercise; however, comparing upper-limb exercise, people with SCI showed higher values.

Purpose: This study aimed to investigate whether carbohydrate ingestion during 3 h long endurance exercise in highly trained cyclists at a rate of 120 g h -1 in 0.8:1 ratio between fructose and glucose-based carbohydrates would result in higher exogenous and lower endogenous carbohydrate oxidation rates as compared to ingestion of 90 g h -1 in 1:2 ratio, which is the currently recommended approach for exercise of this duration., Methods: Eleven male participants (V̇O 2peak 62.6 ± 7 mL kg -1  min -1 , gas exchange threshold (GET) 270 ± 17 W and Respiratory compensation point 328 ± 32 W) completed the study involving 4 experimental visits consisting of 3 h cycling commencing after an overnight fast at an intensity equivalent to 95% GET. During the trials they received carbohydrates at an average rate of 120 or 90 g h -1 in 0.8:1 or 1:2 fructose-maltodextrin ratio, respectively. Carbohydrates were naturally high or low in 13 C stable isotopes enabling subsequent calculations of exogenous and endogenous carbohydrate oxidation rates., Results: Exogenous carbohydrate oxidation rates were higher in the 120 g h -1 condition (120-180 min: 1.51 ± 0.22 g min -1 ) as compared to the 90 g h -1 condition (1.29 ± 0.16 g min -1 ; p = 0.026). Endogenous carbohydrate oxidation rates did not differ between conditions (2.15 ± 0.30 and 2.20 ± 0.33 g min -1 for 120 and 90 g h -1 conditions, respectively; p = 0.786)., Conclusions: The results suggest that carbohydrate ingestion at 120 g h -1 in 0.8:1 fructose-maltodextrin ratio as compared with 90 g h -1 in 1:2 ratio offers higher exogenous carbohydrate oxidation rates but no additional sparing of endogenous carbohydrates. Further studies should investigate potential performance effects of such carbohydrate ingestion strategies., (© 2022. The Author(s).)

Effective storage of excess energy in abdominal subcutaneous adipose tissue during periods of overeating may help attenuate weight-gain-related insulin resistance. The objective of this study was to assess changes in the expression of factors regulating abdominal subcutaneous adipose tissue storage capacity in response to a brief exposure to overeating in nonobese adults. Because exercise can alter the expression of genes involved in regulating adipose tissue storage capacity, we compared the responses to overeating in regular exercisers (EX, n  = 11) and nonexercisers (nonEX, n  = 11). Abdominal subcutaneous adipose tissue samples and oral glucose tolerance tests were performed before and after participants ate 30% above their estimated daily energy requirements for 1 week. Both EX and nonEX gained ∼1 kg ( P  < 0.01), and Matsuda insulin sensitivity index was reduced ∼15% ( P  = 0.04) in both groups. Gene expression of factors involved in lipid metabolism ( HSL, ATGL, DGAT , and PPARγ ) and angiogenesis ( HIF1α and KDR ) were increased ( P  < 0.05), with no differences observed between EX and nonEX. In contrast, protein abundance of these factors did not change. The modest overeating stimulus did not increase markers of inflammation in the systemic circulation or adipose tissue. Overall, our findings indicate that a brief and modest overeating stimulus can impair insulin sensitivity and upregulate genes involved in abdominal adipose tissue storage capacity similarly in exercisers and nonexercisers. ClinicalTrials.gov ID#: NCT02701738.

The purpose of the study was to examine the effects of carbohydrate (CHO) mouth rinsing on autonomic and metabolic recovery as well as cycling performance. Ten male recreational cyclists (age = 30 ± 6 years, VO 2peak = 54.5 ± 8.1 mL·kg -1 ·min -1 ) completed a randomized, double-blind, placebo-controlled, crossover designed study. A CHO or a placebo (PLA) rinse was administered every 12.5% of a work to completion trial (75%W max ). Heart rate variability (lnRMSSD), the respiratory exchange ratio, and plasma epinephrine, norepinephrine, insulin, glucose, free fatty acids (FFA), and lactate were measured pre- and post-exercise. The CHO rinse did not improve time to completion of the test trial (CHO: 4108 ± 307 s, PLA: 4176 ± 374 s, p = 0.545). Further, the CHO rinse did not impact autonomic recovery, as measured by lnRMSSD (p = 0.787) and epinephrine (p = 0.132). Metabolic biomarkers were also unaffected by the CHO rinse, with no differences observed in responses of FFA (p = 0.064), lactate (p = 0.302), glucose (p = 0.113) or insulin (p = 0.408). Therefore, the CHO mouth rinse does not reduce the acute sympathetic response following strenuous exercise and does not result in improvements in cycling time to completion., (© 2022 Cassie M. Williamson-Reisdorph, Emily E. Bechke, Cherilyn McLester, Robert Buresh, Melinda Millard-Stafford, Zackery Green, Rasmus Rooks, Brett Nickerson, Brian M. Kliszczewicz, published by Sciendo.)

Introduction: The AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis that becomes activated by exercise and binds glycogen, an important energy store required to meet exercise-induced energy demands. Disruption of AMPK-glycogen interactions in mice reduces exercise capacity and impairs whole-body metabolism. However, the mechanisms underlying these phenotypic effects at rest and following exercise are unknown. Furthermore, the plasma metabolite responses to an acute exercise challenge in mice remain largely uncharacterized. Methods: Plasma samples were collected from wild type (WT) and AMPK double knock-in (DKI) mice with disrupted AMPK-glycogen binding at rest and following 30-min submaximal treadmill running. An untargeted metabolomics approach was utilized to determine the breadth of plasma metabolite changes occurring in response to acute exercise and the effects of disrupting AMPK-glycogen binding. Results: Relative to WT mice, DKI mice had reduced maximal running speed ( p < 0.0001) concomitant with increased body mass ( p < 0.01) and adiposity ( p < 0.001). A total of 83 plasma metabolites were identified/annotated, with 17 metabolites significantly different ( p < 0.05; FDR<0.1) in exercised (↑6; ↓11) versus rested mice, including amino acids, acylcarnitines and steroid hormones. Pantothenic acid was reduced in DKI mice versus WT. Distinct plasma metabolite profiles were observed between the rest and exercise conditions and between WT and DKI mice at rest, while metabolite profiles of both genotypes converged following exercise. These differences in metabolite profiles were primarily explained by exercise-associated increases in acylcarnitines and steroid hormones as well as decreases in amino acids and derivatives following exercise. DKI plasma showed greater decreases in amino acids following exercise versus WT. Conclusion: This is the first study to map mouse plasma metabolomic changes following a bout of acute exercise in WT mice and the effects of disrupting AMPK-glycogen interactions in DKI mice. Untargeted metabolomics revealed alterations in metabolite profiles between rested and exercised mice in both genotypes, and between genotypes at rest. This study has uncovered known and previously unreported plasma metabolite responses to acute exercise in WT mice, as well as greater decreases in amino acids following exercise in DKI plasma. Reduced pantothenic acid levels may contribute to differences in fuel utilization in DKI mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Belhaj, Lawler, Hawley, Broadhurst, Hoffman and Reinke.)

The discovery of functional brown adipose tissue (BAT) in adult humans and the possibility to recruit beige cells with high thermogenic potential within white adipose tissue (WAT) depots opened the field for new strategies to combat obesity and its associated comorbidities. Exercise training as well as cold exposure and dietary components are associated with the enhanced accumulation of metabolically-active beige adipocytes and BAT activation. Both activated beige and brown adipocytes increase their metabolic rate by utilizing lipids to generate heat via non-shivering thermogenesis, which is dependent on uncoupling protein 1 (UCP1) in the inner mitochondrial membrane. Non-shivering thermogenesis elevates energy expenditure and promotes a negative energy balance, which may ameliorate metabolic complications of obesity and Type 2 Diabetes Mellitus (T2DM) such as insulin resistance (IR) in skeletal muscle and adipose tissue. Despite the recent advances in pharmacological approaches to reduce obesity and IR by inducing non-shivering thermogenesis in BAT and WAT, the administered pharmacological compounds are often associated with unwanted side effects. Therefore, lifestyle interventions such as exercise, cold exposure, and/or specified dietary regimens present promising anchor points for future disease prevention and treatment of obesity and T2DM. The exact mechanisms where exercise, cold exposure, dietary interventions, and pharmacological treatments converge or rather diverge in their specific impact on BAT activation or WAT browning are difficult to determine. In the past, many reviews have demonstrated the mechanistic principles of exercise- and/or cold-induced BAT activation and WAT browning. In this review, we aim to summarize not only the current state of knowledge on the various mechanistic principles of diverse external stimuli on BAT activation and WAT browning, but also present their translational potential in future clinical applications.

The purpose of the study was to assess the accuracy of commonly used GPS/accelerometer-based tracking devices in the estimation of exercise energy expenditure (EEE) during high-intensity intermittent exercise. A total of 13 female soccer players competing at the highest level in Norway (age 20.5 ± 4.3 years; height 168.4 ± 5.1 cm; weight 64.1 ± 5.3 kg; fat free mass 49.7 ± 4.2 kg) completed a single visit test protocol on an artificial grass surface. The test course consisted of walking, jogging, high-speed running, and sprinting, mimicking the physical requirements in soccer. Three commonly used tracking devices were compared against indirect calorimetry as the criterion measure to determine their accuracy in estimating the total energy expenditure. The anaerobic energy consumption (i.e., excess post-exercise oxygen consumption, EPOC) and resting time were examined as adjustment factors possibly improving accuracy. All three devices significantly underestimated the total energy consumption, as compared to the criterion measure ( p = 0.022, p = 0.002, p = 0.017; absolute ICC = 0.39, 0.24 and 0.30, respectively), and showed a systematic pattern with increasing underestimation for higher energy consumption. Excluding EPOC from EEE reduced the bias substantially (all p 's becoming non-significant; absolute ICC = 0.49, 0.54 and 0.49, respectively); however, bias was still present for all tracking devices. All GPS trackers were biased by showing a general tendency to underestimate the exercise energy consumption during high intensity intermittent exercising, which in addition showed a systematic pattern by over- or underestimation during lower or higher exercising intensity. Adjusting for EPOC reduced the bias and provided a more acceptable accuracy. For a more correct EEE estimation further calibration of these devices by the manufacturers is strongly advised by possibly addressing biases caused by EPOC.

Purpose: Low energy availability in males needs more original research to understand its health and performance consequences. The aim of the study was to induce low energy availability in previously healthy male endurance athletes by reducing energy availability by 25% for 14 consecutive days and measure any potential changes in performance, health, mental state or energy markers., Methods: Energy availability was reduced in 12 trained, well-trained and elite endurance athletes by increasing energy expenditure and controlling energy intake. After intervention, health was assessed by blood draw, body composition was measured, energy markers by measuring resting energy expenditure, performance with three specific tests (measuring endurance, agility and explosive power) and two questionnaires were used for psychological assessment (the Three Factor Eating Questionnaire and Well-being questionnaire)., Results: Reduced energy availability (22.4 ± 6.3 kcal/kg FFM/day) caused significantly lower haemoglobin values (t(12) = 2.652, p = 0.022), there was a tendency for lower iron and IGF-1 (p = 0.066 and p = 0.077, respectively). Explosive power was reduced (t(12) = 4.570, p = 0.001), lactate metabolism was altered and athletes reported poorer well-being (t(12) = 2.385, p = 0.036). Cognitive restriction was correlated with energy availability (r = 0.528, p = 0.039)., Conclusion: This is the first research providing direct evidence that suboptimal energy availability negatively impacts explosive power before hormonal changes occur in male endurance athletes. It is also the first to show direct association of low energy availability and higher cognitive restriction. We also observed worse well-being and lower haemoglobin values. 25% of energy availability reduction as not enough to elicit changes in resting energy expenditure., (© 2021. The Author(s).)

Tissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is not fully defined. To understand how tissues independently and collectively respond to timed exercise, we applied a systems biology approach. We mapped and compared global metabolite responses of seven different mouse tissues and serum after an acute exercise bout performed at different times of the day. Comparative analyses of intra- and inter-tissue metabolite dynamics, including temporal profiling and blood sampling across liver and hindlimb muscles, uncovered an unbiased view of local and systemic metabolic responses to exercise unique to time of day. This comprehensive atlas of exercise metabolism provides clarity and physiological context regarding the production and distribution of canonical and novel time-dependent exerkine metabolites, such as 2-hydroxybutyrate (2-HB), and reveals insight into the health-promoting benefits of exercise on metabolism., Competing Interests: Declaration of interests J.R.Z. is an Advisory Board member for Cell Metabolism. The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The study aimed to identify and quantify the metabolites profile and metabolic pathways in human muscle tissue engaged during exhaustive high-intensity cycling exercise. Seven healthy physically active men performed a graded exercise test and an exhaustive supramaximal effort at 115% of maximal aerobic power with muscles biopsies performed in rest and immediately after exhaustion for quantifying of muscle metabolites changes by 1 H-NMR spectroscopy. The time until exhaustion (tlim) recorded was 224.7 ± 35.5 s whereas the muscle pH at exhaustion was 6.48 ± 0.05. A total of 54 metabolites were identified and quantified. The most enriched and impacted pathways included: beta oxidation of very long chain fatty acids, mitochondrial electron transport chain, alanine aspartate, and glutamate metabolism, citric acid cycle, arginine biosynthesis, propanoate metabolism, threonine and 2-oxobutanoate degradation and pyruvate metabolism. In addition, the muscle concentrations in Post exercise, compared to Pre increased significantly (p < 0.0398) for fumarate (42.0%), succinate (101.2%), glucose (249.7%), lactate (122.8%), O-acetylcarnitine (164.7%), glycerol (79.3%), AMP (288.2%), 2-oxobutyrate (121.0%), and methanol (58.5%), whereas decreased significantly (p < 0.010) for creatine phosphate (-70.2%), ADP (-56.5%), carnitine (-33.5%), and glutamate (-42.3%). Only the succinate was significantly correlated with tlim (r = -0.76; p = 0.0497). Besides the classical expected contribution of glycolytic and phosphagen energetic pathways, it was demonstrated that the high-intensity exercise is also associated with pathways indicatives of amino acid and fatty acid oxidation metabolisms, highlighting the inverse relation between changes in the intramuscular succinate levels and tlim., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Previous studies suggest that sex differences in lipid metabolism exist with females demonstrating a higher utilization of lipids during exercise, which is mediated partly by increased utilization of muscle triglycerides. However, whether these changes in lipid metabolism contribute directly to endurance exercise performance is unclear. Therefore, the objective of this study was to investigate the contribution of exercise substrate metabolism to sex differences in endurance exercise capacity (EEC) in mice. Male and female C57BL/6-NCrl mice were subjected to an EEC test until exhaustion on a motorized treadmill. The treadmill was set at a 10% incline, and the speed gradually increased from 10.2 m/min to 22.2 m/min at fixed intervals for up to 2.5 h. Tissues and blood were harvested in mice immediately following the EEC. A cohort of sedentary, non-exercised male and female mice were used as controls. Females outperformed males by ~25% on the EEC. Serum levels of both fatty acids and ketone bodies were ~50% higher in females at the end of the EEC. In sedentary female mice, skeletal muscle triglyceride content was significantly greater compared to sedentary males. Gene expression analysis demonstrated that genes involved in skeletal muscle fatty acid oxidation were significantly higher in females with no changes in genes associated with glucose uptake or ketone body oxidation. The findings suggest that female mice have a higher endurance exercise capacity and a greater ability to mobilize and utilize fatty acids for energy., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Exercise improves the insulin sensitivity of glucose uptake in skeletal muscle. Due to that, exercise has become a cornerstone treatment for type 2 diabetes mellitus (T2DM). The mechanisms by which exercise improves skeletal muscle insulin sensitivity are, however, incompletely understood. We conducted a systematic review to identify all genes whose gain or loss of function alters skeletal muscle glucose uptake. We subsequently cross-referenced these genes with recently generated data sets on exercise-induced gene expression and signaling. Our search revealed 176 muscle glucose-uptake genes, meaning that their genetic manipulation altered glucose uptake in skeletal muscle. Notably, exercise regulates the expression or phosphorylation of more than 50% of the glucose-uptake genes or their protein products. This included many genes that previously have not been associated with exercise-induced insulin sensitivity. Interestingly, endurance and resistance exercise triggered some common but mostly unique changes in expression and phosphorylation of glucose-uptake genes or their protein products. Collectively, our work provides a resource of potentially new molecular effectors that play a role in the incompletely understood regulation of muscle insulin sensitivity by exercise., (© 2021 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals LLC.)

The accumulation of lactate in muscle and blood during high-intensity exercise is negatively correlated with the duration exercise can be sustained. Removal of lactate is a key component of acute recovery between consecutive bouts of such exercise. Low-intensity exercise enhances recovery by accelerating lactate turnover in metabolically active tissues, largely mediated by blood flow to these tissues. Therefore, the purpose of this research was to clarify if L-citrulline, a nutritional supplement purported to promote vasodilation via enhanced nitric oxide availability, would augment the removal of blood lactate during active recovery (AR). L-citrulline ingestion will augment the rate of blood lactate concentration decrease during AR, reduce the oxygen-cost of submaximal exercise, and increase time-to-exhaustion and peak oxygen uptake (V̇O2peak) during a test of maximal aerobic power. Healthy university students (five males & five females) participated in this double-blind, randomized, placebo-controlled study. Participants exercised on a cycle ergometer at submaximal steady-state intensities followed by progressively increasing intensity to exhaustion, 10 min of AR, and then supramaximal intensity exercise to exhaustion. Oxygen uptake was measured throughout the trial and blood lactate was sampled repeatedly during AR. The protocol elicited very high peak blood lactate concentrations after exercise (11.3 + 1.3 mmol/L). L-citrulline supplementation did not significantly alter blood lactate kinetics during AR, the oxygen cost of exercise, V̇O2peak, or time-to-exhaustion. Despite a strong theoretical basis by which L-citrulline could augment lactate removal from the blood, L-citrulline supplementation showed no effect as an exercise-recovery supplement.

The aim of this study was to compare the effect of dynamic (DRT) and isometric (IRT) resistance training on glycemic homeostasis, lipid profile, and nitric oxide (NO) in hemodialysis (HD) patients. Patients were randomly distributed into 3 groups: control ( n  = 65), DRT ( n  = 65), and IRT ( n  = 67). Patients assessed before and after the intervention period were tested for fasting blood glucose, glycated hemoglobin, oral glucose tolerance test, insulin resistance, lipid profile, leptin, insulin, adiponectin, C-reactive protein, and NO . Patients underwent to strength and body composition assessments. Subjects allocated in both DRT and IRT groups took part in a 24-week resistance training program, 3 times per week. Each training session was approximately 1 hour before dialysis and consisted of 3 sets of 8-12 repetitions at low intensity. Total workload was higher in the DRT as compared with the IRT. This heightened workload related to better glycemic homeostasis in HD patients as measured by regulation of insulin, adiponectin, and leptin, while improveing triglycerides, free-fat mass, and muscle strength. Additionally, NO levels were increased in the DRT group. NO was significantly correlated with glucose intolerance ( r  = -0.42, p  = 0.0155) and workload ( r  = 0.46, p  = 0.0022). The IRT group only improved strength ( p  < 0.05). Twenty-four weeks of DRT improved glycemic homeostasis, lipid profile, and NO in HD patients. Although IRT seems to play an important role in increasing strength, DRT might be a better choice to promote metabolic adjustments in HD patients. Clinical trial: http://www.ensaiosclinicos.gov.br/rg/RBR-3gpg5w. Novelty: DRT might be a better choice for metabolic improvements in patients with chronic kidney disease (CKD). Exercise-training might treat metabolic imbalance in CKD patients.

The study aimed to investigate the relationship between anaerobic capacity, mechanical and anaerobic contribution during the 30-s Wingate Anaerobic Test (30sWAnT). After familiarization, fifteen, male recreational mountain biking practitioners underwent the following sequence of tests: 1) a graded exercise test to determine maximal oxygen uptake and associated intensity i V ˙ O 2 m a x ; 2 and 3) supramaximal exhaustive effort at 115% of iVO 2max and 30sWAnT, performed randomly. The glycolytic and phosphagen pathways measured during the supramaximal effort were significantly correlated with peak power (r = 0.85; p < 0.01 and r = 0.57; p = 0.02, respectively), mean power (r = 0.78; p < 0.01 and r = 0.69; p < 0.01, respectively), and total work (r = 0.78; p < 0.01 and r = 0.69; p< 0.02, respectively) measured during the 30sWAnT. A significant correlation was also found between anaerobic capacity and peak power (r = 0.88; p < 0.01), mean power (r = 0.89; p < 0.01), and total work (r = 0.89; p < 0.01). Additionally, anaerobic capacity estimated during the supramaximal effort and the anaerobic contribution measured during the 30sWAnT were not different (p = 0.44) and presented significant good reliability and association (ICC = 0.84; p = 0.001) and good agreement, evidenced by the mean of differences and 95% limits of agreement near to zero (mean bias = 0.11). The results suggest that glycolytic and phosphagen capacity were associated with mechanical performance in the 30sWAnT. In addition, anaerobic contribution during the 30sWAnT seems to be valid for estimating anaerobic capacity in recreational mountain bike cyclists, as well as to estimate the glycolytic and phosphagen contributions., (© 2021 Rodrigo Araujo Bonetti de Poli, Willian Eiji Miyagi, Alessandro Moura Zagatto, published by Sciendo.)

Exogenous ketone supplementation and whole-body cooling (WBC) have shown to independently influence exercise metabolism. Whether readily available ketone salts, with and without WBC, would provide similar metabolic benefits during steady-state aerobic and time-trial performances was investigated. Nine active males (VO 2peak : 56.3 ± 2.2 mL·kg -1 ·min -1 ) completed three single-blind exercise sessions preceded by: (1) ingestion of placebo (CON), (2) ketone supplementation (0.3 g·kg -1 β-OHB) (KET), and (3) ketone supplementation with WBC (KETCO). Participants cycled in steady-state (SS, 60% W max ) condition for 30-min, immediately followed by a 15-min time trial (TT). Skin and core temperature, cardio-metabolic, and respiratory measures were collected continuously, whereas venous blood samples were collected before and after supplementation, after SS and TT. Venous β-OHB was elevated, while blood glucose was lower, with supplementation vs. CON ( p < 0.05). TT power output was not different between conditions ( p = 0.112, CON: 190 ± 43.5 W, KET: 185 ± 40.4 W, KETCO: 211 ± 50.7 W). RER was higher during KETCO (0.97 ± 0.09) compared to both CON (0.88 ± 0.04, p = 0.012) and KET (0.88 ± 0.05, p = 0.014). Ketone salt supplementation and WBC prior to short-term exercise sufficiently increase blood β-OHB concentrations, but do not benefit metabolic shifts in fuel utilization or improve time trial performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Clark, Munten, Herzig and Gagnon.)

Introduction: Military leaders must understand how modern military equipment loads affect trade-offs between movement speed and physiological strain to optimize pacing strategies., Purpose: To evaluate the effects of load carried in a recently developed military backpack on the walking speed and cardiometabolic responses of dismounted warfighters., Methods: Fifteen soldiers (1 woman, 14 men; age, 22 ± 2 years; height, 173 ± 7 cm; body mass (BM), 73 ± 10 kg) completed incremental walking tests with four external load conditions (0, 22, 44, or 66% BM) using the US Army's newest backpack: the Modular Lightweight Load-Carrying Equipment 4000 (MOLLE 4000). Oxygen uptake (V̇O 2 ) and heart rate (HR) were evaluated relative to maximal values (V̇O 2max and HR max respectively). Testing ceased when participants completed the highest tested speed (1.97 m s -1 ), exceeded a respiratory exchange ratio (RER) of 1.00, or reached volitional exhaustion., Results: Peak speed significantly decreased (p < 0.03) with successively heavier loads (0% BM, 1.95 ± 0.06 m s -1 ; 22% BM, 1.87 ± 0.10 m s -1 ; 44% BM, 1.69 ± 0.13 m s -1 ; 66% BM, 1.48 ± 0.13 m s -1 ). Peak V̇O 2 was significantly lower (p < 0.01) with 0% BM (47 ± 5% V̇O 2max ) than each load (22% BM, 58 ± 8% V̇O 2max ; 44% BM, 63 ± 10% V̇O 2max ; 66% BM, 61 ± 11% V̇O 2max ). Peak HR was significantly lower (p < 0.01) with 0% BM (71 ± 5% HR max ) versus each load (22% BM, 83 ± 6% HR max ; 44% BM, 87 ± 6% HR max ; 66% BM, 88 ± 6% HR max )., Conclusion: Overburdened warfighters suffer severe impairments in walking speed even when carrying recently developed military load carriage equipment. Our results suggest that the relative work intensity of heavy load carriage may be better described when expressed relative to HR max versus V̇O 2max ., (Published by Elsevier Ltd.)

Background: High-intensity interval training (HIIT) induces similar or even superior adaptations compared to continuous endurance training. Indeed, just 6 HIIT sessions over 2 weeks significantly improves maximal oxygen uptake (VO 2max ), submaximal exercise fat oxidation, and endurance performance. Whether even faster adaptations can be achieved with HIIT is not known. Thus, we aimed to determine whether 2 sessions of HIIT per day, separated by 3 h, every other day for 5 days (double HIIT (HIIT-D), n = 15) could increase VO 2max , submaximal exercise fat oxidation, and endurance capacity as effectively as 6 sessions of HIIT over 2 weeks (single HIIT (HIIT-S), n = 13)., Methods: Each training session consisted of 10 × 60 s of cycling at 100% of VO 2max interspersed with 75 s of low-intensity cycling at 60 watt (W). Pre- and post-training assessments included VO 2max , time to exhaustion at ∼80% of VO 2max , and 60-min cycling trials at ∼67% of VO 2max ., Results: Similar increases (p < 0.05) in VO 2max (HIIT-D: 7.7% vs. HIIT-S: 6.0%, p > 0.05) and endurance capacity (HIIT-D: 80.1% vs. HIIT-S: 79.2%, p > 0.05) were observed. Submaximal exercise carbohydrate oxidation was reduced in the 2 groups after exercise training (HIIT-D: 9.2%, p = 0.014 vs. HIIT-S: 18.8%, p = 0.012) while submaximal exercise fat oxidation was significantly increased in HIIT-D (15.5%, p = 0.048) but not in HIIT-S (9.3%, p = 0.290)., Conclusion: Six HIIT sessions over 5 days was as effective in increasing VO 2max and endurance capacity and was more effective in improving submaximal exercise fat oxidation than 6 HIIT sessions over 2 weeks., (Copyright © 2020. Production and hosting by Elsevier B.V.)

Aim: To investigate the in vivo skeletal muscle metabolism in patients with β-enolase deficiency (GSDXIII) during exercise, and the effect of glucose infusion., Methods: Three patients with GSDXIII and 10 healthy controls performed a nonischemic handgrip test as well as an incremental cycle ergometer test measuring maximal oxidative consumption (VO 2max ) and a 1-hour submaximal cycle test at an intensity of 65% to 75% of VO 2max . The patients repeated the submaximal exercise after 2 days, where they received a 10% iv-glucose supplementation., Results: Patients had lower VO 2max than healthy controls, and two of three patients had to stop prematurely during the intended 1-hour submaximal exercise test. During nonischemic forearm test, all patients were able to produce lactate in normal amounts. Glucose infusion had no effect on patients' exercise capacity., Conclusions: Patients with GSDXIII experience exercise intolerance and episodes of myoglobinuria, even to the point of needing renal dialysis, but still retain an almost normal anaerobic metabolic response to submaximal intensity exercise. In accordance with this, glucose supplementation did not improve exercise capacity. The findings show that GSDXIII, although causing episodic rhabdomyolysis, is one of the mildest metabolic myopathies affecting glycolysis., Competing Interests: The authors declare no potential conflict of interest., (© 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Pilates has been known as exercise intervention that improves the function of pelvic floor muscle (PFM) associated with impacting urinary incontinence (UI). This study investigated the effect of Pilates on UI in Korean women by determining the change in functional movement of PFM (FMP) and metabolic profiles. UI group with Pilates (UIP, n = 13) participated in 8-weeks Oov Pilates program, and 8 subjects were assigned to Control and UI group with no Pilates (UINP), respectively. Before and after 8 weeks, plasma samples were collected from all participants, and ultrasonography was used to measure the functional change of PFM for calculating FMP ratio. Plasma samples were analyzed by mass spectrometry to identify the change of metabolic features. After 8-weeks intervention, FMP ratio was remarkably decreased in UIP (48.1% ↓, p < 0.001), but not in Control and UINP ( p > 0.05). In metabolic features, L-Glutamine ( m / z : 147.07 [M + H] + ), L-Cystathionine ( m / z : 240.09 [M + NH 4 ] + ), L-Arginine ( m / z : 197.1 [M + Na] + ), and L-1-Pyrroline-3-hydroxy-5-carboxylate ( m / z : 147.07 [M + NH 4 ] + ) were significantly elevated solely in UIP ( p < 0.001). Our study elucidated that Pilates can ameliorate the FMP and enhance the specific metabolic characteristics, which was potentially associated with invigorated PFM contractility to effectively control the bladder base and continence.

Team sports players are required to perform repeated bouts of short-term high-intensity actions during the games. The present study aimed to examine the effects of a novel repeated sprint ability protocol (20×15 m) and compare it with the impact of a more traditional repeated sprint ability protocol (10×30 m). Twelve male elite Lithuanian basketball players (age 21.0 ± 2.0 y, body height 1.90 ± 0,07 m, body mass 86.2 ± 5.8 kg and training experience 12.0 ± 1.9 y) competing in the Lithuanian National Basketball Championship participated in this study. Participants completed three bouts of each repeated sprint protocol interspersed with 5 minutes of recovery. Results showed that the 20×15 m protocol caused a significant decrease in total sprint time (most likely; mean changes (%) with ± 90% of confidence limits, -9.4%; ± 0.7%) and a large decrease in blood lactate (most likely, -39.2%; ±12.8%) compared to the 10×30 m protocol. Despite small differences, the fatigue index presented a similar trend (possibly decrease, -23.7%; ± 38.8%). The exercise heart rate showed a very similar trend with trivial differences between the two protocols. The 20×15 m protocol presented a lower heart rate during recovery with small magnitude. Overall, the present study showed that the 20×15 m protocol seemed to be more representative of the specific basketball demands. Coaches should be aware that RSA training during the in-season may be an adequate stimulus to improve high-intensity runs and muscle power in high-level players., (© 2021 Bruno Figueira, Bruno Gonçalves, Eduardo Abade, Rūtenis Paulauskas, Nerijus Masiulis, Paulius Kamarauskas, Jaime Sampaio, published by Sciendo.)

The purpose of this systematic review was to synthesize and evaluate current literature examining the effects of exercise on postprandial fat oxidation, as well as to provide future direction. A quantitative review was performed using meta-analytic methods. A moderator analysis was performed to investigate potential variables that could influence the effect of exercise on postprandial fat oxidation. Fifty-six effects from 26 studies were retrieved. There was a moderate effect of exercise on postprandial fat oxidation (Cohen's d = 0.58 (95% CI, 0.39 to 0.78)). Moderator analysis revealed that sex, age, weight status, training status, exercise type, exercise intensity, timing of exercise, and composition of the meal challenge significantly affected the impact of prior exercise on postprandial fat oxidation. The moderator analysis also indicated that most previous studies have investigated the impact of prior moderate-intensity endurance exercise on postprandial fat oxidation in young, healthy, lean men. Suggested priorities for future research in this area include ( i ) an examination of sex differences in and/or female-specific aspects of postprandial metabolism; ( ii ) a comprehensive evaluation of exercise modalities, intensities, and durations; and ( iii ) a wider variety of test meal compositions, especially those with higher fat content. Novelty A systematic review of the impact of exercise on postprandial fat oxidation was performed using meta-analytic methods. Analysis revealed a moderate effect of exercise on postprandial fat oxidation. The presented data support a need for future studies to investigate sex differences and to include comprehensive evaluations of exercise modalities, intensities, and duration.

The majority of human energy metabolism occurs in skeletal muscle mitochondria emphasizing the importance of understanding the regulation of myocellular mitochondrial function. The transcriptional co-activator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) has been characterized as a major factor in the transcriptional control of several mitochondrial components. Thus, PGC-1α is often described as a master regulator of mitochondrial biogenesis as well as a central player in regulating the antioxidant defense. However, accumulating evidence suggests that PGC-1α is also involved in the complex regulation of mitochondrial quality beyond biogenesis, which includes mitochondrial network dynamics and autophagic removal of damaged mitochondria. In addition, mitochondrial reactive oxygen species production has been suggested to regulate skeletal muscle insulin sensitivity, which may also be influenced by PGC-1α. This review aims to highlight the current evidence for PGC-1α-mediated regulation of skeletal muscle mitochondrial function beyond the effects on mitochondrial biogenesis as well as the potential PGC-1α-related impact on insulin-stimulated glucose uptake in skeletal muscle. Novelty PGC-1α regulates mitochondrial biogenesis but also has effects on mitochondrial functions beyond biogenesis. Mitochondrial quality control mechanisms, including fission, fusion, and mitophagy, are regulated by PGC-1α. PGC-1α-mediated regulation of mitochondrial quality may affect age-related mitochondrial dysfunction and insulin sensitivity.

Purpose: Prior studies exploring the reliability of peak fat oxidation (PFO) and the intensity that elicits PFO (FAT MAX ) are often limited by small samples. This study characterised the reliability of PFO and FAT MAX in a large cohort of healthy men and women., Methods: Ninety-nine adults [49 women; age: 35 (11) years; [Formula: see text]O 2 peak: 42.2 (10.3) mL·kg BM -1 ·min -1 ; mean (SD)] completed two identical exercise tests (7-28 days apart) to determine PFO (g·min -1 ) and FAT MAX (%[Formula: see text]O 2 peak) by indirect calorimetry. Systematic bias and the absolute and relative reliability of PFO and FAT MAX were explored in the whole sample and sub-categories of: cardiorespiratory fitness, biological sex, objectively measured physical activity levels, fat mass index (derived by dual-energy X-ray absorptiometry) and menstrual cycle status., Results: No systematic bias in PFO or FAT MAX was found between exercise tests in the entire sample (- 0.01 g·min -1 and 0%[Formula: see text]O 2 peak, respectively; p > 0.05). Absolute reliability was poor [within-subject coefficient of variation: 21% and 26%; typical errors: ± 0.06 g·min -1 and × / ÷ 1.26%[Formula: see text]O 2 peak; 95% limits of agreement: ± 0.17 g·min -1 and × / ÷ 1.90%[Formula: see text]O 2 peak, respectively), despite high (r = 0.75) and moderate (r = 0.45) relative reliability for PFO and FAT MAX, respectively. These findings were consistent across all sub-groups., Conclusion: Repeated assessments are required to more accurately determine PFO and FAT MAX .

Introduction: We investigated the effects of a supervised progressive sprint interval training (SIT) and moderate-intensity continuous training (MICT) on adipocyte morphology and adipose tissue metabolism and function; we also tested whether the responses were similar regardless of baseline glucose tolerance and sex., Research Design and Methods: 26 insulin-resistant (IR) and 28 healthy participants were randomized into 2-week-long SIT (4-6×30 s at maximum effort) and MICT (40-60 min at 60% of maximal aerobic capacity (VO 2peak )). Insulin-stimulated glucose uptake and fasting-free fatty acid uptake in visceral adipose tissue (VAT), abdominal and femoral subcutaneous adipose tissues (SATs) were quantified with positron emission tomography. Abdominal SAT biopsies were collected to determine adipocyte morphology, gene expression markers of lipolysis, glucose and lipid metabolism and inflammation., Results: Training increased glucose uptake in VAT (p<0.001) and femoral SAT (p<0.001) and decreased fatty acid uptake in VAT (p=0.01) irrespective of baseline glucose tolerance and sex. In IR participants, training increased adipose tissue vasculature and decreased CD36 and ANGPTL4 gene expression in abdominal SAT. SIT was superior in increasing VO 2peak and VAT glucose uptake in the IR group, whereas MICT reduced VAT fatty acid uptake more than SIT., Conclusions: Short-term training improves adipose tissue metabolism both in healthy and IR participants independently of the sex. Adipose tissue angiogenesis and gene expression was only significantly affected in IR participants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sprint interval training (SIT) has demonstrated reductions in fat mass through potential alterations in postexercise metabolism. This study examined whether exercising in the fasted or fed state affects postexercise metabolism following acute SIT. Ten active males performed a bout of modified SIT (8 × 15-s sprints; 120 s recovery) in both a fasted (FAST) and fed (FED) state. Gas exchange was collected through 3 h postexercise, appetite perceptions were measured using a visual analog scale, and energy intake was recorded using dietary food logs. There was no difference in energy expenditure between conditions at any time point ( p > 0.329) or in total session energy expenditure (FED: 514.8 ± 54.9 kcal, FAST: 504.0 ± 74.3 kcal; p = 0.982). Fat oxidation at 3 h after exercise was higher in FED (0.110 ± 0.04 g·min -1 ) versus FAST (0.069 ± 0.02 g·min -1 ; p = 0.013) though not different between conditions across time ( p > 0.340) or in total postexercise fat oxidation (FED: 0.125 ± 0.04 g·min -1 , FAST: 0.105 ± 0.02 g·min -1 ; p = 0.154). Appetite perceptions were lower in FED (-4815.0 ± 4098.7 mm) versus FAST (-707.5 ± 2010.4 mm, p = 0.022); however, energy intake did not differ between conditions ( p = 0.429). These results demonstrate the fasted or fed state does not augment postexercise metabolism following acute SIT in a way that would favour fat loss following training. Novelty Energy expenditure was similar between conditions, while fat oxidation was significantly greater in FED at 3 h after exercise. Appetite perceptions were significantly lower in FED; however, energy intake was not different between conditions. Current findings suggest that performing SIT in the fed or fasted state would not affect fat loss following training.

We hypothesized that probiotic supplementation (PRO) increases the absorption and oxidation of orally ingested maltodextrin during 2 h endurance cycling, thereby sparing muscle glycogen for a subsequent time trial (simulating a road race). Measurements were made of lipid and carbohydrate oxidation, plasma metabolites and insulin, gastrointestinal (GI) permeability, and subjective symptoms of discomfort. Seven male cyclists were randomized to PRO (bacterial composition given in methods) or placebo for 4 wk, separated by a 14-day washout period. After each period, cyclists consumed a 10% maltodextrin solution (initial 8 mL/kg bolus and 2 mL/kg every 15 min) while exercising for 2 h at 55% maximal aerobic power output, followed by a 100-kJ time trial. PRO resulted in small increases in peak oxidation rates of the ingested maltodextrin (0.84 ± 0.10 vs. 0.77 ± 0.09 g/min; P = 0.016) and mean total carbohydrate oxidation (2.20 ± 0.25 vs. 1.87 ± 0.39 g/min; P = 0.038), whereas fat oxidation was reduced (0.40 ± 0.11 vs. 0.55 ± 0.10 g/min; P = 0.021). During PRO, small but significant increases were seen in glucose absorption, plasma glucose, and insulin concentration and decreases in nonesterified fatty acid and glycerol. Differences between markers of GI damage and permeability and time-trial performance were not significant ( P > 0.05). In contrast to the hypothesis, PRO led to minimal increases in absorption and oxidation of the ingested maltodextrin and small reductions in fat oxidation, whereas having no effect on subsequent time-trial performance.

This 12-week exercise intervention study assessed changes in cardiorespiratory fitness (CRF), energy expenditure (EE), and substrate utilisation at rest and during exercise in obese, black South African (SA) women and explored associations with changes in body composition. Black SA women (body mass index: 30-40 kg·m -2 , age: 20-35 years) were randomised into control (CTL; n = 15, maintaining usual activity) or exercise (EXE; n = 20; 12 weeks, 4 days·week -1 , 40-60 min·day -1 at >70% peak heart rate) groups. Pre- and post-intervention testing included peak oxygen consumption, resting and steady state (50% peak oxygen consumption) EE, respiratory exchange, and body composition (dual-energy X-ray absorptiometry). Dietary intake (4-day) and daily step-count (ActivPAL, activPAL3c; PAL Technologies Ltd, Glasgow, UK) was collected at pre-testing and at 4, 8, and 12 weeks. EXE increased peak oxygen consumption (24.9 ± 2.4 to 27.6 ± 3.4 mL·min -1 ·kg -1 ; p < 0.001) and steady state fat oxidation rates (7.5 ± 2.5 to 9.0 ± 2.7 mg·min -1 ·kg -1 fat-free soft tissue mass; p = 0.003) (same relative exercise intensity). CTL remained unchanged ( p > 0.05). EXE reduced proportional gynoid fat mass (percentage total fat mass, p = 0.002). Baseline resting carbohydrate oxidation rates ( p = 0.036) and steady state fat oxidation rates ( p = 0.021) explained 60.6% of the variability in Δgynoid fat mass ( p < 0.001) in EXE. This 12-week exercise intervention improved CRF and steady state fat oxidation rates. Greater reliance on fat oxidation at baseline promoted proportional reductions in gynoid, not visceral, fat mass in response to exercise training. Novelty Combined exercise training in obese black South African women increased cardiorespiratory fitness and rates of fat oxidation during steady state exercise. Exercise training reduced proportional gynoid, not visceral, fat, potentially representing an ethnic/sex-specific response. Baseline substrate utilisation (resting and steady state exercise (50% peak oxygen uptake)) predicted changes in gynoid fat mass.

While the timing of food intake is important, it is unclear whether the effects of exercise on energy metabolism are restricted to unique time windows. As circadian regulation is key to controlling metabolism, understanding the impact of exercise performed at different times of the day is relevant for physiology and homeostasis. Using high-throughput transcriptomic and metabolomic approaches, we identify distinct responses of metabolic oscillations that characterize exercise in either the early rest phase or the early active phase in mice. Notably, glycolytic activation is specific to exercise at the active phase. At the molecular level, HIF1α, a central regulator of glycolysis during hypoxia, is selectively activated in a time-dependent manner upon exercise, resulting in carbohydrate exhaustion, usage of alternative energy sources, and adaptation of systemic energy expenditure. Our findings demonstrate that the time of day is a critical factor to amplify the beneficial impact of exercise on both metabolic pathways within skeletal muscle and systemic energy homeostasis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fructose metabolism is generally held to occur essentially in cells of the small bowel, the liver, and the kidneys expressing fructolytic enzymes (fructokinase, aldolase B and a triokinase). In these cells, fructose uptake and fructolysis are unregulated processes, resulting in the generation of intracellular triose phosphates proportionate to fructose intake. Triose phosphates are then processed into lactate, glucose and fatty acids to serve as metabolic substrates in other cells of the body. With small oral loads, fructose is mainly metabolized in the small bowel, while with larger loads fructose reaches the portal circulation and is largely extracted by the liver. A small portion, however, escapes liver extraction and is metabolized either in the kidneys or in other tissues through yet unspecified pathways. In sedentary subjects, consumption of a fructose-rich diet for several days stimulates hepatic de novo lipogenesis, increases intrahepatic fat and blood triglyceride concentrations, and impairs insulin effects on hepatic glucose production. All these effects can be prevented when high fructose intake is associated with increased levels of physical activity. There is also evidence that, during exercise, fructose carbons are efficiently transferred to skeletal muscle as glucose and lactate to be used for energy production. Glucose and lactate formed from fructose can also contribute to the re-synthesis of muscle glycogen after exercise. We therefore propose that the deleterious health effects of fructose are tightly related to an imbalance between fructose energy intake on one hand, and whole-body energy output related to a low physical activity on the other hand., (© 2019 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objectives: The present study verified the effect of moderate-to-high-intensity aerobic exercise on the endocrine response profile and adipose tissue in young healthy men with different phenotype characteristics., Design: Eighteen men were divided into three experimental groups with defined body components and specific physical fitness: Endurance phenotype - EP (n = 6; low body mass; low fat content; aerobic endurance trained), Athletic phenotype - AP (n = 6; high body mass; low fat content, resistance trained), Obesity phenotype - OP (n = 6; high body mass; high fat content, untrained)., Methods: The participants performed an progressive exercise protocol on a treadmill (30% VO2max, 50% VO2max, 70% VO2max), separated by 45 s of passive rest for blood collection., Results: Plasma glucose oxidation increased in relation to exercise intensity, but to a greater extent in the AP group. The free fatty acids' plasma level decreased with a rise in exercise intensity, but with different kinetics in particular phenotypes. Plasma growth hormone increased after the cessation of exercise and was significantly higher in all groups 45 min into recovery compared to resting values. Plasma insulin decreased during exercise in all groups, but in the OP, the decrease was blunted., Conclusions: The results indicate that the rate of lipolysis, hormonal and metabolic response to aerobic exercise depends on the individuals' phenotype. Thus, exercise type, duration and intensity have to be strictly individualized in relation to phenotype in order to reach optimal metabolic benefits.

Interleukin-6 (IL-6), IL-15, and heat shock protein 72 (Hsp72) are molecules that have significant metabolic effects on glucose and fat metabolism and a cell's stress response. The aim of this study is to determine serum levels of these molecules in runners after a long-distance trail run. Serum IL-15 levels after such endurance events have not been investigated yet. Blood samples were collected from 37 athletes (11 female, 26 male) before and after a 35-km trail run, with a total climb of 940 m. Serum was obtained from the samples, and IL-6, IL-15, and Hsp72 levels were measured from using the sandwich ELISA method. The athletes completed the race in 308.3 ± 37.4 min on average. After the race, the mean serum IL-6, IL-15, and Hsp72 concentrations increased 13.2-fold, 2.22-fold, and 1.6-fold, respectively ( p < 0.001, p < 0.001, and p = 0.039, respectively). This is the first study to demonstrate the increase in serum IL-15 levels following an acute endurance exercise. In addition to IL-15, we report that IL-6 and soluble Hsp72 levels also increased significantly following a 35-km trail run. Since these molecules are involved in regulating glucose and fat metabolism, significant increases of IL-6, IL-15, and soluble Hsp72 may have health benefits that may be associated with long-distance trail runs, which are becoming more popular worldwide.

The current study investigated whether a single bout of concurrent exercise (Ex Rx) at Third Age Academies (TAAs) in Rio de Janeiro City meets the American College of Sports Medicine (ACSM) guidelines for energy cost and metabolic intensity in older adults. Nine subjects (5 males and 4 females, 63-80 years of age) visited the laboratory for clinical screening and for anthropometrical, resting, and maximal oxygen uptake assessments. Thereafter, subjects performed an Ex Rx circuit consisting of a single circuit alternating aerobic and resistance exercises with outdoor exercise equipment using body mass as the load (total of 9 exercises, 1-2 sets of 15 repetitions). Expired gases were collected via a metabolic cart during exercise bouts. The mean observed energy cost value of 169.1 kcal was slightly greater than the minimum value of 150 kcal reported in the ACSM guidelines ( p = 0.018). Like energy cost, all the intensity markers adopted to analyze the physiological strain induced by the Ex Rx circuit significantly exceeded their reference values for moderate intensity (reference values: 3.2 METs (mean observed value = 4.6 METs, p = 0.002); 40% of oxygen uptake reserve (mean observed value = 51.5%, p = 0.040); 40% of heart rate reserve (mean observed value = 64.1%, p < 0.001)), according to the ACSM guidelines. In conclusion, a single bout of Ex Rx circuit performed at TAAs in Rio de Janeiro City was able to induce a physiological strain (i.e., energy cost and intensity) compatible with ACSM recommendations for eliciting health benefits among older adults.

Background: The ketogenic diet is becoming a popular nutritional model among athletes. However, the relationship between its use and metabolism during exercise seems to have not been fully investigated., Methods: The aim of the study was to assess the effects of a four-week ketogenic diet (KD) on fat and carbohydrate (CHO) utilization during an incremental cycling test (ICT) in CrossFit-trained female (n = 11) and male (n = 11) athletes. During the ICT (while consuming the customary diet and after the KD), oxygen uptake and carbon dioxide exhalation were registered, and CHO and fat utilization as well as energy expenditure were calculated., Results: In males, the KD led to an increase in fat utilization (g·min - 1 ·kg FFM - 1 and % oxidation). It was particularly noticeable at exercise intensities up to 80% of VO 2max . An increase in the area under the curve (AUC) was seen in males but not in females at up to ≤65% VO 2max of fat utilization., Conclusions: Male CrossFit-trained athletes seem to be more prone to shifts in macronutrient utilization (in favor of fat utilization) during submaximal intensity exercise under a ketogenic diet than are female athletes., Trial Registration: Clinical Trials Gov, NCT03665948 . Registered 11 September 2018 (retrospectively registered).

Endurance performance is the result of optimal training targeting cardiovascular, metabolic, and peripheral muscular adaptations and is coupled to effective nutrition strategies via the use of macronutrient manipulations surrounding training and potential supplementation with ergogenic aids. It is important to note that training and nutrition may differ according to the individual needs of the athlete and can markedly impact the physiological response to training. Herein, we discuss various aspects of endurance training adaptations, nutritional strategies and their contributions to towards performance.

Carbon isotopes of breath CO 2 vary depending on diet and fuel substrate used. This study examined if exercise-induced δ 13 C-CO 2 changes in substrate utilization were distinguishable from baseline δ 13 C-CO 2 variations in a population with uncontrolled diet, and compared hair isotope values and food logs to develop an isotope model of diet. Study participants included nine women with diverse Body Mass Index (BMI), age, ancestry, exercise history, and diet. Breath samples were collected prior to and up to 12 h after a 5- or 10 K walk/run. Indirect calorimetry was measured with a smartphone-enabled mobile colorimetric device, and a field-deployable isotope analyzer measured breath δ 13 C-CO 2 values. Diet was assessed by food logs and δ 13 C, δ 15 N of hair samples. Post-exercise δ 13 C-CO 2 values increased by 0.54 ± 1.09‰ (1 sd, n = 9), implying enhanced carbohydrate burning, while early morning δ 13 C-CO 2 values were lower than daily averages (p = 0.0043), indicating lipid burning during overnight fasting. Although diurnal δ 13 C-CO 2 variation (1.90 ± 0.77‰) and participant baseline range (3.06‰) exceeded exercise-induced variation, temporal patterns distinguished exercise from dietary isotope effects. Hair δ 13 C and δ 15 N values were consistent with a new dietary isotope model. Notwithstanding the small number of participants, this study introduces a novel combination of techniques to directly monitor energy balance in free-living individuals.