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Metabolomics incorporates the study of metabolites that are produced and released through physiological processes at both the systemic and cellular levels. Biological compounds at the metabolite level are of paramount interest in the sport and exercise sciences, although research in this field has rarely been referred to with the global 'omics terminology. Commonly studied metabolites in exercise science are notably within cellular pathways for adenosine triphosphate production such as glycolysis (e.g., pyruvate and lactate), β-oxidation of free fatty acids (e.g., palmitate) and ketone bodies (e.g., β-hydroxybutyrate). Non-targeted metabolomic technologies are able to simultaneously analyse the large numbers of metabolites present in human biological samples such as plasma, urine and saliva. These analytical technologies predominately employ nuclear magnetic resonance spectroscopy and chromatography coupled to mass spectrometry. Performing experiments based on non-targeted methods allows for systemic metabolite changes to be analysed and compared to a particular physiological state (e.g., pre-/post-exercise) and provides an opportunity to prospect for metabolite signatures that offer beneficial information for translation into an exercise science context, for both elite performance and public health monitoring. This narrative review provides an introduction to non-targeted metabolomic technologies and discusses current and potential applications in sport and exercise science.

Background: A better understanding of hypoxia-induced changes in substrate utilisation can facilitate the development of nutritional strategies for mountaineers, military personnel and athletes during exposure to altitude. However, reported metabolic responses are currently divergent. As such, this systematic review and meta-analysis aims to determine the changes in substrate utilisation during exercise in hypoxia compared with normoxia and identify study characteristics responsible for the heterogeneity in findings., Methods: A total of six databases (PubMed, the Cochrane Library, MEDLINE, SPORTDiscus, PsychINFO, and CINAHL via EBSCOhost) were searched for published original studies, conference proceedings, abstracts, dissertations and theses. Studies were included if they evaluated respiratory exchange ratio (RER) and/or carbohydrate or fat oxidation during steady state exercise matched for relative intensities in normoxia and hypoxia (normobaric or hypobaric). A random-effects meta-analysis was performed on outcome variables. Meta-regression analysis was performed to investigate potential sources of heterogeneity., Results: In total, 18 studies were included in the meta-analysis. There was no significant change in RER during exercise matched for relative exercise intensities in hypoxia, compared with normoxia (mean difference: 0.01, 95% CI: -0.02 to 0.05; n = 31, p = 0.45). Meta-regression analysis suggests that consumption of a pre-exercise meal (p < 0.01) and a higher exercise intensity (p = 0.04) when exposed to hypoxia may increase carbohydrate oxidation compared with normoxia., Conclusions: Exposure to hypoxia did not induce a consistent change in the relative contribution of carbohydrate or fat to the total energy yield during exercise matched for relative intensities, compared with normoxia. The direction of these responses appears to be mediated by the consumption of a pre-exercise meal and exercise intensity.

Exercise facilitates weight control, partly through effects on appetite regulation. Single bouts of exercise induce a short-term energy deficit without stimulating compensatory effects on appetite, whilst limited evidence suggests that exercise training may modify subjective and homeostatic mediators of appetite in directions associated with enhanced meal-induced satiety. However, a large variability in responses exists between individuals. This article reviews the evidence relating to how adiposity, sex, and habitual physical activity modulate exercise-induced appetite, energy intake, and appetite-related hormone responses. The balance of evidence suggests that adiposity and sex do not modify appetite or energy intake responses to acute or chronic exercise interventions, but individuals with higher habitual physical activity levels may better adjust energy intake in response to energy balance perturbations. The effect of these individual characteristics and behaviours on appetite-related hormone responses to exercise remains equivocal. These findings support the continued promotion of exercise as a strategy for inducing short-term energy deficits irrespective of adiposity and sex, as well as the ability of exercise to positively influence energy balance over the longer term. Future well-controlled studies are required to further ascertain the potential mediators of appetite responses to exercise.

High-altitude exposure induces a negative energy balance by increasing resting energy expenditure and decreasing energy intake. This diminished energy intake is likely caused by altitude-induced anorexia and can have detrimental effects for those travelling to high-altitude. We aimed to investigate whether altering the macronutrient composition of breakfast could attenuate altitude-induced anorexia and augment energy intake at high-altitude. Twelve healthy men (aged 26 (8) years, body mass index 23.9 (2.7) kg·m -2 ) completed two, 305min experimental trials at 4300m simulated altitude (~11.7% O 2 ). After an overnight fast, participants entered a normobaric hypoxic chamber and rested for one hour, before receiving either a high fat (HF; 60% fat, 25% carbohydrate) or an isocaloric high carbohydrate (HC; 60% carbohydrate, 25% fat) breakfast. One hour after breakfast, participants performed 60min of treadmill walking at 50% of relative V̇O 2max . An ad-libitum buffet meal was consumed 1h 30min after exercise. Appetite perceptions, blood samples and substrate oxidation rates were measured throughout. A significantly higher area under the curve for composite appetite score was observed during exercise in HF (40 (12) mm·h -1 ) compared with HC (30 (17) mm·h -1 , P=0.036). During exercise, lower insulin concentrations (P=0.013) and elevated acylated ghrelin concentrations (P=0.048) were observed in HF compared with HC. After exercise there was no significant difference in composite appetite score (P=0.356), acylated ghrelin (P=0.229) or insulin (P=0.513) between conditions. Energy intake at the buffet did not significantly differ between conditions (P=0.384). A HF breakfast attenuated appetite suppression during exercise at 4300m simulated altitude, however ad-libitum energy intake did not increase., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to characterize the immediate and extended effect of acute exercise on hunger, energy intake, and circulating acylated ghrelin concentrations using a large data set of homogenous experimental trials and to describe the variation in responses between individuals., Methods: Data from 17 of our group's experimental crossover trials were aggregated yielding a total sample of 192 young, healthy males. In these studies, single bouts of moderate to high-intensity aerobic exercise (69% ± 5% V˙O2 peak; mean ± SD) were completed with detailed participant assessments occurring during and for several hours postexercise. Mean hunger ratings were determined during (n = 178) and after (n = 118) exercise from visual analog scales completed at 30-min intervals, whereas ad libitum energy intake was measured within the first hour after exercise (n = 60) and at multiple meals (n = 128) during the remainder of trials. Venous concentrations of acylated ghrelin were determined at strategic time points during (n = 118) and after (n = 89) exercise., Results: At group level, exercise transiently suppressed hunger (P < 0.010, Cohen's d = 0.77) but did not affect energy intake. Acylated ghrelin was suppressed during exercise (P < 0.001, Cohen's d = 0.10) and remained significantly lower than control (no exercise) afterward (P < 0.024, Cohen's d = 0.61). Between participants, there were notable differences in responses; however, a large proportion of this spread lay within the boundaries of normal variation associated with biological and technical assessment error., Conclusion: In young men, acute exercise suppresses hunger and circulating acylated ghrelin concentrations with notable diversity between individuals. Care must be taken to distinguish true interindividual variation from random differences within normal limits.

Acute exposure to high altitude (>3500 m) is associated with marked changes in appetite regulation and substrate oxidation but the effects of lower altitudes are unclear. This study examined appetite, gut hormone, energy intake and substrate oxidation responses to breakfast ingestion and exercise at simulated moderate and severe altitudes compared with sea-level. Twelve healthy males (mean ± SD; age 30 ± 9years, body mass index 24.4 ± 2.7 kg·m -2 ) completed in a randomised crossover order three, 305 min experimental trials at a simulated altitude of 0 m, 2150 m (∼15.8% O 2 ) and 4300 m (∼11.7% O 2 ) in a normobaric chamber. Participants entered the chamber at 8am following a 12 h fast. A standardised breakfast was consumed inside the chamber at 1 h. One hour after breakfast, participants performed a 60 min treadmill walk at 50% of relative V˙O 2max . An ad-libitum buffet meal was consumed 1.5 h after exercise. Blood samples were collected prior to altitude exposure and at 60, 135, 195, 240 and 285 min. No trial based differences were observed in any appetite related measure before exercise. Post-exercise area under the curve values for acylated ghrelin, pancreatic polypeptide and composite appetite score were lower (all P < 0.05) at 4300 m compared with sea-level and 2150 m. There were no differences in glucagon-like peptide-1 between conditions (P = 0.895). Mean energy intake was lower at 4300 m (3728 ± 3179 kJ) compared with sea-level (7358 ± 1789 kJ; P = 0.007) and 2150 m (7390 ± 1226 kJ; P = 0.004). Proportional reliance on carbohydrate as a fuel was higher (P = 0.01) before breakfast but lower during (P = 0.02) and after exercise (P = 0.01) at 4300 m compared with sea-level. This study suggests that altitude-induced anorexia and a subsequent reduction in energy intake occurs after exercise during exposure to severe but not moderate simulated altitude. Acylated ghrelin concentrations may contribute to this effect., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Carbohydrate mouth rinsing can improve endurance exercise performance and is most ergogenic when exercise is completed in the fasted state. This strategy may also be beneficial to increase exercise capacity and the energy deficit achieved during moderate-intensity exercise relevant to weight control when performed after an overnight fast. Eighteen healthy men (mean (SD); age, 23 (4) years; body mass index, 23.1 (2.4) kg·m -2 ) completed a familiarisation trial and 3 experimental trials. After an overnight fast, participants performed 60 min of treadmill walking at a speed that equated to a rating of perceived exertion of 13 ("fairly hard"). Participants manually adjusted the treadmill speed to maintain this exertion. Mouth rinses for the experimental trials contained either a 6.4% maltodextrin solution with sweetener (CHO), a taste-matched placebo (PLA), or water (WAT). Appetite ratings were collected using visual analogue scales and exercise energy expenditure and substrate oxidation were calculated from online gas analysis. Increased walking distance during CHO and PLA induced greater energy expenditure compared with WAT (mean difference (90% confidence interval); 79 (60) kJ, P = 0.035, d = 0.24; and 90 (63) kJ, P = 0.024, d = 0.27, respectively). Appetite area under the curve was lower in CHO and PLA than WAT (8 (6) mm, P = 0.042, d = 0.43; and 6 (8) mm, P = 0.201, d = 0.32, respectively). Carbohydrate oxidation was higher in CHO than PLA and WAT (7.3 (6.7) g, P = 0.078, d = 0.47; and 10.1 (6.5) g, P = 0.015, d = 0.81, respectively). This study provides novel evidence that mouth rinsing with a sweetened solution may promote a greater energy deficit during moderate-exertion walking exercise by increasing energy expenditure and decreasing appetite. A placebo effect may have contributed to these benefits.

In lean individuals, acute aerobic exercise is reported to transiently suppress sensations of appetite, suppress blood concentrations of acylated ghrelin (AG), and increase glucagon-like peptide-1 (GLP-1) and peptide-YY (PYY). Findings in overweight/obese individuals have yet to be synthesised. In this systematic review and meta-analysis, we quantified the effects that acute exercise has on AG and total PYY and GLP-1 in overweight/obese individuals. The potential for body mass index (BMI) to act as a moderator for AG was also explored. Six published studies (73 participants, 78% male, mean BMI: 30.6 kg·m -2 ) met the inclusion criteria. Standardised mean differences (SMDs) and standard errors were extracted for AG and total PYY and GLP-1 concentrations in control and exercise trials and synthesised using a random effects meta-analysis model. BMI was the predictor in metaregression for AG. Exercise moderately suppressed AG area-under-the-curve concentrations (pooled SMD: -0.34, 95% CI: -0.53 to -0.15). The magnitude of this reduction was greater for higher mean BMIs (pooled metaregression slope: -0.04 SMD/kg·m -2 (95% CI: -0.07 to 0.00)). Trivial SMDs were obtained for total PYY (0.10, 95% CI: -0.13 to 0.31) and GLP-1 (-0.03, 95% CI: -0.18 to 0.13). This indicates that exercise in overweight/obese individuals moderately alters AG in a direction that could be associated with decreased hunger and energy intake. This trial is registered with PROSPERO: CRD42014006265., Competing Interests: The authors declare that they have no competing interests.

Weight loss is the result of a sustained negative energy balance, which is typically achieved by decreasing food intake and/or increasing physical activity. Current evidence suggests that acute energy deficits of ~4820 kJ elicit contrasting homeostatic responses when induced by exercise and food restriction but the response to government-recommended energy deficits is unknown. Twelve healthy men (mean(SD): age 24(5) years, body mass index 23.8(2.7) kg⋅m(-2), maximum oxygen uptake 55.4(9.1) mL⋅kg(-1)⋅min(-1)) completed three 8 h trials (control (Con), exercise-induced energy deficit (Ex-Def) and food restriction (Food-Def)) separated by 1 week. Thirty minutes of cycling at 64.5(3.2)% of maximum oxygen uptake was performed in Ex-Def from 0 to 0.5 h, which induced an energy deficit of 1469(256) kJ. An equivalent energy deficit was induced in Food-Def (1478(275) kJ) by reducing the energy content of standardised test meals at 1 h and 4 h. Appetite ratings, acylated ghrelin and peptide YY3-36 concentrations were measured throughout each trial. An ad libitum meal was provided at 7 h. Appetite was higher in Food-Def than Ex-Def from 4 to 8 h (P = 0.033) and tended to be higher across the entire 8 h trial (P = 0.059). However, energy intake at the ad libitum meal did not differ between trials (P = 0.634; Con 4376 (1634); Food-Def 4481 (1846); Ex-Def 4217 (1850) kJ). Acylated ghrelin was not related to changes in appetite but plasma PYY3-36 concentrations were higher in Ex-Def than Food-Def (P < 0.05) and negatively correlated with changes in appetite across the entire 8 h trial (P = 0.037). An energy deficit of ~1475 kJ stimulated compensatory increases in appetite when induced via calorie restriction but not when achieved by an acute bout of exercise. Appetite responses were associated with changes in plasma PYY3-36 but not acylated ghrelin concentrations and did not influence subsequent energy intake., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Recent years have witnessed significant interest from both the scientific community and the media regarding the influence of exercise on subsequent appetite and energy intake responses. This review demonstrates a consensus among the majority of scientific investigations that an acute bout of land-based endurance exercise does not stimulate any compensatory increases in appetite and energy intake on the day of exercise. Alternatively, preliminary evidence suggests that low volume, supramaximal exercise may stimulate an increase in appetite perceptions during the subsequent hours. In accordance with the apparent insensitivity of energy intake to exercise in the short term, the daily energy balance response to exercise appears to be primarily determined by the energy cost of exercise. This finding supports the conclusions of recent training studies that the energy expenditure of exercise is the strongest predictor of fat loss during an exercise programme.

Sprint interval exercise improves several health markers but the appetite and energy balance response is unknown. This study compared the effects of sprint interval and endurance exercise on appetite, energy intake and gut hormone responses. Twelve healthy males [mean (SD): age 23 (3) years, body mass index 24.2 (2.9) kg m(-2), maximum oxygen uptake 46.3 (10.2) mL kg(-1) min(-1)] completed three 8 h trials [control (CON), endurance exercise (END), sprint interval exercise (SIE)] separated by 1 week. Trials commenced upon completion of a standardised breakfast. Sixty minutes of cycling at 68.1 (4.3) % of maximum oxygen uptake was performed from 1.75-2.75 h in END. Six 30-s Wingate tests were performed from 2.25-2.75 h in SIE. Appetite ratings, acylated ghrelin and peptide YY (PYY) concentrations were measured throughout each trial. Food intake was monitored from buffet meals at 3.5 and 7 h and an overnight food bag. Appetite (P < 0.0005) and acylated ghrelin (P < 0.002) were suppressed during exercise but more so during SIE. Peptide YY increased during exercise but most consistently during END (P < 0.05). Acylated ghrelin was lowest in the afternoon of SIE (P = 0.018) despite elevated appetite (P = 0.052). Exercise energy expenditure was higher in END than that in SIE (P < 0.0005). Energy intake was not different between trials (P > 0.05). Therefore, relative energy intake (energy intake minus the net energy expenditure of exercise) was lower in END than that in CON (15.7 %; P = 0.006) and SIE (11.5 %; P = 0.082). An acute bout of endurance exercise resulted in lower appetite perceptions in the hours after exercise than sprint interval exercise and induced a greater 24 h energy deficit due to higher energy expenditure during exercise.