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PURPOSE: To determine whether combined ingestion of maltodextrin and fructose during 150 min of cycling exercise would lead to exogenous carbohydrate oxidation rates higher than 1.1 g.min. METHODS: Eight trained cyclists VO2max: 64.1 +/- 3.1 mL.kg.min) performed three exercise trials in a random order. Each trial consisted of 150 min cycling at 55% maximum power output (64.2+/-3.5% VO2max) while subjects received a solution providing either 1.8 g.min of maltodextrin (MD), 1.2 g.min of maltodextrin + 0.6 g.min of fructose (MD+F), or plain water. To quantify exogenous carbohydrate oxidation, corn-derived MD and F were used, which have a high natural abundance of C. RESULTS: Peak exogenous carbohydrate oxidation (last 30 min of exercise) rates were approximately 40% higher with combined MD+F ingestion compared with MD only ingestion (1.50+/-0.07 and 1.06+/-0.08 g.min, respectively, P<0.05). Furthermore, the average exogenous carbohydrate oxidation rate during the last 90 min of exercise was higher with combined MD+F ingestion compared with MD alone (1.38+/-0.06 and 0.96+/-0.07 g.min, respectively, P<0.05). CONCLUSIONS: The present study demonstrates that with ingestion of large amounts of maltodextrin and fructose during cycling exercise, exogenous carbohydrate oxidation can reach peak values of approximately 1.5 g.min, and this is markedly higher than oxidation rates from ingesting maltodextrin alone. [ABSTRACT FROM AUTHOR]

Identification of a number of the genes that cause skeletal dysplasias has helped clinicians to provide accurate diagnoses, genetic counseling, and pre-natal diagnosis for this complex group of disorders. This review considers how some of the recent advances in human and murine genetics have led to an increased understanding of normal bone development and, in particular, the processes of skeletal patterning and endochondral ossification. [ABSTRACT FROM AUTHOR]

There is little evidence that body size alters exogenous glucose oxidation rates during exercise. This study assessed whether larger people oxidize more exogenous glucose during exercise than smaller people. Fifteen cyclists were allocated into two groups based on body mass (SMALL, <70 kg body mass, n = 9, two females) or (LARGE, >70 kg body mass, n = 6) matched for lactate threshold (SMALL: 2.3 ± 0.4 W/kg, LARGE: 2.3 ± 0.3 W/kg). SMALL completed 120 min of cycling at 95% of lactate threshold1. LARGE completed two trials in a random order, one at 95% of lactate threshold1 (thereby exercising at the same relative intensity [RELATIVE]) and one at an absolute intensity matched to SMALL (ABSOLUTE). In all trials, cyclists ingested 90 g/hr of 13C-enriched glucose. Total exogenous glucose oxidation was (mean ± SD) 33 ± 8 g/hr in SMALL versus 45 ± 13 g/hr in LARGE-RELATIVE (mean difference: 13 g/hr, 95% confidence interval [2, 24] g/hr, p = .03). Large positive correlations were observed for measures of exogenous carbohydrate oxidation versus body size (body mass, height, and body surface area; e.g., body surface area vs. peak exogenous glucose oxidation, r = .85, 95% confidence interval [.51, .95], p < .01). When larger athletes reduced the intensity from RELATIVE to ABSOLUTE, total exogenous glucose oxidation was 39 ± 7 g/hr (p = .43 vs. LARGE-RELATIVE). In conclusion, the capacity for exogenous glucose oxidation is, on average, higher in larger athletes than smaller athletes during exercise. The extent to which this is due to higher absolute exercise intensity requires further research, but body size may be a consideration in tailoring sports nutrition guidelines for carbohydrate intake during exercise.

Exercise is an essential component of body mass management interventions. Overnight-fasted exercise (FASTex) acutely enhances fat oxidation compared with fed exercise (FEDex). However, consistent FASTex training does not typically further enhance body mass loss, suggesting the induction of energy compensation responses. The present study aimed to test the effects of FASTex or FEDex on the components of energy balance (i.e., energy intake (EI), energy expenditure (EE), and appetite) and interstitial glucose metrics across four days., Methods: Twelve (10 men, 2 women) healthy, physically active participants (age 22.6 + 1.2 years (mean ± SD); BMI 22.5 ± 2.8 kg ⋅ m -2 ) were studied twice, across four days, after a 75-min run either FASTex or FEDex. Daily EI was obtained after subtracting leftovers from the provided food. Daily fasting appetite was measured by visual analogue scales. Activity- and total- EE (AEE & TEE, respectively) were estimated by combining heart rate and accelerometry. Continuous glucose monitoring was used to capture daily interstitial glucose metrics and Likert scales were utilised to quantify fatigue, stress, sleep quality, and muscle soreness levels., Results: No differences between conditions were observed for EI (FASTex = 15.0 ± 0.1 vs FEDex = 15.0 ± 0.4 MJ⋅day -1 ; p = 0.865), AEE (FASTex = 7.6 ± 1.1 vs FEDex 7.8 ± 1.3 MJ⋅day -1 ; p = 0.223) and TEE (FASTex = 15.9 ± 3.4 vs 14.9 ± 4.5 MJ⋅day -1 ; p = 0.136). Additionally, no condition effects for appetite (p > 0.05) and interstitial glucose (p = 0.074) were observed., Conclusion: FASTex did not differ from FEDex in the response of components of energy balance or interstitial glucose across four days, suggesting that both exercise approaches could be used interchangeably., 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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ingested galactose can enhance postexercise liver glycogen repletion when combined with glucose but effects on muscle glycogen synthesis are unknown. In this double-blind randomized study participants [7 men and 2 women; V̇o 2max : 51.1 (8.7) mL·kg -1 ·min -1 ] completed three trials of exhaustive cycling exercise followed by a 4-h recovery period, during which carbohydrates were ingested at the rate of 1.2 g·kg -1 ·h -1 comprising glucose (GLU), galactose (GAL) or galactose + glucose (GAL + GLU; 1:2 ratio). The increase in vastus lateralis skeletal-muscle glycogen concentration during recovery was higher with GLU relative to GAL + GLU [contrast: +50 mmol·(kg DM) -1 ; 95%CL 10, 89; P = 0.021] and GAL [+46 mmol·(kg DM) -1 ; 95%CL 8, 84; P = 0.024] with no difference between GAL + GLU and GAL [-3 mmol·(kg DM) -1 ; 95%CL -44, 37; P = 0.843]. Plasma glucose concentration in GLU was not significantly different vs. GAL + GLU (+ 0.41 mmol·L -1 ; 95%CL 0.13, 0.94) but was significantly lower than GAL (-0.75 mmol·L -1 ; 95%CL -1.34, -0.17) and also lower in GAL vs. GAL + GLU (-1.16 mmol· -1 ; 95%CL -1.80, -0.53). Plasma insulin was higher in GLU + GAL and GLU compared with GAL but not different between GLU + GAL and GLU. Plasma galactose concentration was higher in GAL compared with GLU (3.35 mmol·L -1 ; 95%CL 3.07, 3.63) and GAL + GLU (3.22 mmol·L -1 ; 95%CL 3.54, 2.90) with no difference between GLU + GAL (0.13 mmol·L -1 ; 95%CL -0.11, 0.37) and GLU. Compared with galactose or a galactose + glucose blend, glucose feeding was more effective in postexercise muscle glycogen synthesis. Comparable muscle glycogen synthesis was observed with galactose-glucose coingestion and exclusive galactose-only ingestion. NEW & NOTEWORTHY Postexercise galactose-glucose coingestion or exclusive galactose-only ingestion resulted in a lower rate of skeletal-muscle glycogen replenishment compared with exclusive glucose-only ingestion. Comparable muscle glycogen synthesis was observed with galactose-glucose coingestion and exclusive galactose-only ingestion.

The effectiveness of exercise to reduce body mass is typically modest, partially due to energy compensation responses which may be linked to energy substrate availability around exercise. The present study aimed to investigate the effect of manipulating post-exercise energy substrate availability (high carbohydrate/low fat [HCLF] or low carbohydrate/high fat [LCHF] energy replacement) on energy balance components in the short-term (i.e., appetite, energy intake (EI) and energy expenditure (EE))., Methods: Appetite, EI, activity- and total- EE were measured in twelve healthy, young (21.0 ± 2.3 years) physically active participants (10 men, 2 women) on two occasions across 4 days after a 75-min run and an isocaloric energy replacement drink (HCLF and LCHF). Appetite was measured daily by visual analogue scales, EI was calculated by subtracting the energy content of food leftovers from a provided food package, activity- and total- EE determined by heart-rate accelerometery., Results: Composite appetite ratings between days were lower in HCLF (62.4 ± 12) compared to LCHF (68.3 ± 8.9 mm; p = 0.048). No differences between conditions were detected for EI. Cumulative activity-EE (HCLF=  20.9 ± 3.7, LCHF=  16.9 ± 3.1 MJ; p = 0.037), but not total-EE (HCLF=  44.6 ± 7.7, LCHF=  39.9 ± 4.7 MJ; p = 0.060), was higher for the HCLF condition than the LCHF across the measurement period., Conclusion: Compared with low carbohydrate/high fat, immediate post-exercise energy replacement with a high carbohydrate/low fat drink resulted in higher short-term activity energy expenditure and lower appetite ratings., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Branched-chain amino acids (BCAA) and carbohydrate (CHO) are commonly recommended postexercise supplements. However, no study has examined the interaction of CHO and BCAA ingestion on myofibrillar protein synthesis (MyoPS) rates following exercise. We aimed to determine the response of MyoPS to the co-ingestion of BCAA and CHO following an acute bout of resistance exercise. Ten resistance-trained young men completed two trials in counterbalanced order, ingesting isocaloric drinks containing either 30.6-g CHO plus 5.6-g BCAA (B + C) or 34.7-g CHO alone following a bout of unilateral, leg resistance exercise. MyoPS was measured postexercise with a primed, constant infusion of L-[ring13C6] phenylalanine and collection of muscle biopsies pre- and 4 hr postdrink ingestion. Blood samples were collected at time points before and after drink ingestion. Serum insulin concentrations increased to a similar extent in both trials (p > .05), peaking at 30 min postdrink ingestion. Plasma leucine (514 ± 34 nmol/L), isoleucine (282 ± 23 nmol/L), and valine (687 ± 33 nmol/L) concentrations peaked at 0.5 hr postdrink in B + C and remained elevated for 3 hr during exercise recovery. MyoPS was ∼15% greater (95% confidence interval [-0.002, 0.028], p = .039, Cohen's d = 0.63) in B + C (0.128%/hr ± 0.011%/hr) than CHO alone (0.115%/hr ± 0.011%/hr) over the 4 hr postexercise period. Co-ingestion of BCAA and CHO augments the acute response of MyoPS to resistance exercise in trained young males.

Prolonged low energy availability, which is the underpinning aetiology of the Relative Energy Deficiency in Sport and the Female and Male Athlete Triad frameworks, can have unfavourable impacts on both health and performance in athletes. Energy availability is calculated as energy intake minus exercise energy expenditure, expressed relative to fat free mass. The current measurement of energy intake is recognized as a major limitation for assessing energy availability due to its reliance on self-report methods, in addition to its short-term nature. This article introduces the application of the energy balance method for the measurement of energy intake, within the context of energy availability. The energy balance method requires quantification of the change in body energy stores over time, with concurrent measurement of total energy expenditure. This provides an objective calculation of energy intake, which can then be used for the assessment of energy availability. This approach, the Energy Availability - Energy Balance (EA EB ) method, increases the reliance on objective measurements, provides an indication of energy availability status over longer periods and removes athlete burden to self-report energy intake. Implementation of the EA EB method could be used to objectively identify and detect low energy availability, with implications for the diagnosis and management of Relative Energy Deficiency in Sport and the Female and Male Athlete Triad., (© 2023. The Author(s).)

The importance of carbohydrate as a fuel source for exercise and athletic performance is well established. Equally well developed are dietary carbohydrate intake guidelines for endurance athletes seeking to optimize their performance. This narrative review provides a contemporary perspective on research into the role of, and application of, carbohydrate in the diet of endurance athletes. The review discusses how recommendations could become increasingly refined and what future research would further our understanding of how to optimize dietary carbohydrate intake to positively impact endurance performance. High carbohydrate availability for prolonged intense exercise and competition performance remains a priority. Recent advances have been made on the recommended type and quantity of carbohydrates to be ingested before, during and after intense exercise bouts. Whilst reducing carbohydrate availability around selected exercise bouts to augment metabolic adaptations to training is now widely recommended, a contemporary view of the so-called train-low approach based on the totality of the current evidence suggests limited utility for enhancing performance benefits from training. Nonetheless, such studies have focused importance on periodizing carbohydrate intake based on, among other factors, the goal and demand of training or competition. This calls for a much more personalized approach to carbohydrate recommendations that could be further supported through future research and technological innovation (e.g., continuous glucose monitoring). Despite more than a century of investigations into carbohydrate nutrition, exercise metabolism and endurance performance, there are numerous new important discoveries, both from an applied and mechanistic perspective, on the horizon., (© 2022. The Author(s).)

Coingestion of glucose and galactose has been shown to enhance splanchnic extraction and metabolism of ingested galactose at rest; effects during exercise are unknown. This study examined whether combined ingestion of galactose and glucose during exercise enhances exogenous galactose oxidation. Fourteen endurance-trained male and female participants [age, 27 (5) yr; V̇o 2peak , 58.1 (7.0) mL·kg -1 ·min -1 ] performed cycle ergometry for 150 min at 50% peak power on four occasions, in a randomized counterbalanced manner. During exercise, they ingested beverages providing carbohydrates at rates of 0.4 g.min -1 galactose (GAL), 0.8 g.min -1 glucose (GLU), and on two occasions 0.8 g.min -1 total galactose-glucose (GAL + GLU; 1:1 ratio). Single-monosaccharide 13 C-labeling (*) was used to calculate independent (GAL, GLU, GAL* + GLU, and GAL + GLU*) and combined (GAL* + GLU*, COMBINE) exogenous-monosaccharide oxidation between exercise. Plasma galactose concentrations with GAL + GLU [0.4 mmol.L; 95% confidence limits (CL): 0.1, 0.6] were lower (contrast: 0.5 mmol.L; 95% CL: 0.2, 0.8; P < 0.0001) than when GAL alone (0.9 mmol.L; 95% CL: 0.7, 1.2) was ingested. Exogenous carbohydrate oxidation with GAL alone (0.31 g·min -1 ; 95% CL: 0.28, 0.35) was marginally reduced (contrast: 0.05 g·min -1 ; 95% CL: -0.09, 0.00007; P = 0.01) when combined with glucose (GAL* + GLU 0.27 g·min -1 ; 0.24, 0.30). Total combined exogenous-carbohydrate oxidation (COMBINE: 0.57 g·min -1 ; 95% CL: 0.49, 0.64) was similar (contrast: 0.02 g·min -1 ; 95% CL: -0.05, 0.09; P = 0.63) when compared with isoenergetic GLU (0.55 g·min -1 ; 95% CL: 0.52, 0.58). In conclusion, coingestion of glucose and galactose did not enhance exogenous galactose oxidation during exercise. When combined, isoenergetic galactose-glucose ingestion elicited similar exogenous-carbohydrate oxidation to glucose suggesting galactose-glucose blends are a valid alternative for glucose as an exogenous-carbohydrate source during exercise. NEW & NOTEWORTHY Glucose and galactose coingestion blunted the galactosemia seen with galactose-only ingestion during exercise. Glucose and galactose coingestion did not enhance the oxidation of ingested galactose during exercise. Combined galactose-glucose (1:1 ratio) ingestion was oxidized to a similar extent as isoenergetic glucose-only ingestion during exercise. Galactose-glucose blends are a viable exogenous carbohydrate energy source for ingestion during exercise.

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).)

Background: Prolonged sitting is associated with increased risk of obesity, type 2 diabetes and cardiovascular disease. Occupational sitting accounts for up to 50 h/week for employees. This pilot study assessed the acceptability of stair climbing as an interruption to sitting throughout working hours, and provided preliminary data of the effects on glucose and lipid profiles., Methods: A quasi-experimental design was conducted involving 16 sedentary office workers (five females and 11 males) for intervention (n = 8) and control groups (n = 8) with mean age of 36.38 (5.58). For the eight-week intervention, a continuous four-floor stair climb and descent was performed eight times/day spread evenly over the working day. A prompt to climb was presented on the participant's computer eight times/day. Participants in the experimental group recorded daily floors climbed and steps (measured using pedometers) in a weekly log sheet. Blood samples were collected pre and post intervention to test effects on fasting glucose and 2 h plasma glucose, triglycerides, and total (TC), LDL and HDL cholesterol. Experimental participants were interviewed at the end of the study. The Wilcoxon signed rank test was used to compare the median changes (pre-post) of the dependent variables., Results: On average, the experimental group climbed 121 floors/week when prompted. There were significant reductions in fasting blood glucose, TC and LDL, as well as the derived measures of 'bad' cholesterol and the TC/HDL ratio in the experimental group. Post-experimental interviews indicated that the interruption to sitting was well tolerated., Conclusion: Prompted stair climbing activity had impacts on health outcomes and was found acceptable to employees at work., Trial Registration: Ethics for this study was approved by Science, Technology, Engineering and Mathematics Ethical Review Committee, University of Birmingham with ethics reference number ERN&#95;15&#95;0491., (© 2022. The Author(s).)

Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases 1-5 . However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear 6 . Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2 + cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are also observed in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Whole-body fat oxidation during exercise can be measured non-invasively during athlete profiling. Gaps in understanding exist in the relationships between fat oxidation during incremental fasted exercise and skeletal muscle parameters, endurance performance, and fat oxidation during prolonged fed-state exercise., Methods: Seventeen endurance-trained males underwent a (i) fasted, incremental cycling test to assess peak whole-body fat oxidation (PFO), (ii) resting vastus lateralis microbiopsy, and (iii) 30-min maximal-effort cycling time-trial preceded by 2-h of fed-state moderate-intensity cycling to assess endurance performance and fed-state metabolism on separate occasions within one week., Results: PFO (0.58 ± 0.28 g . min -1 ) was associated with vastus lateralis citrate synthase activity (69.2 ± 26.0 μmol . min -1. g -1 muscle protein, r = 0.84, 95% CI 0.58, 0.95, P < 0.001), CD36 abundance (16.8 ± 12.6 μg . g -1 muscle protein, r s  = 0.68, 95% CI 0.31, 1.10, P = 0.01), pre-loaded 30-min time-trial performance (251 ± 51 W, r = 0.76, 95% CI 0.40, 0.91, P = 0.001; 3.2 ± 0.6 W . kg -1 , r = 0.62, 95% CI 0.16, 0.86, P = 0.01), and fat oxidation during prolonged fed-state cycling (r = 0.83, 95% CI 0.57, 0.94, P < 0.001). Addition of PFO to a traditional model of endurance (peak oxygen uptake, power at 4 mmol . L -1 blood lactate concentration, and gross efficiency) explained an additional ~ 2.6% of variation in 30-min time-trial performance (adjusted R 2  = 0.903 vs. 0.877)., Conclusion: These associations suggest non-invasive measures of whole-body fat oxidation during exercise may be useful in the physiological profiling of endurance athletes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mitochondria are critical to skeletal muscle contractile function and metabolic health. Short-term periods of step reduction (SR) are associated with alterations in muscle protein turnover and mass. However, the effects of SR on mitochondrial metabolism/muscle oxidative metabolism and insulin-mediated signaling are unclear. We tested the hypothesis that the total and/or phosphorylated protein content of key skeletal muscle markers of mitochondrial/oxidative metabolism, and insulin-mediated signaling would be altered over 7 days of SR in young healthy males. Eleven, healthy, recreationally active males (means ± SE, age: 22 ± 1 yr, BMI: 23.4 ± 0.7 kg·m 2 ) underwent a 7-day period of SR. Immediately before and following SR, fasted-state muscle biopsy samples were acquired and analyzed for the assessment of total and phosphorylated protein content of key markers of mitochondrial/oxidative metabolism and insulin-mediated signaling. Daily step count was significantly reduced during the SR intervention (13,054 ± 833 to 1,192 ± 99 steps·day -1 , P < 0.001). Following SR, there was a significant decline in maximal citrate synthase activity (fold change: 0.94 ± 0.08, P < 0.05) and a significant increase in the protein content of p-glycogen synthase (P-GS S641 ; fold change: 1.47 ± 0.14, P < 0.05). No significant differences were observed in the total or phosphorylated protein content of other key markers of insulin-mediated signaling, oxidative metabolism, mitochondrial function, or mitochondrial dynamics (all P > 0.05). These results suggest that short-term SR reduces the maximal activity of citrate synthase, a marker of mitochondrial content, without altering the total or phosphorylated protein content of key markers of skeletal muscle mitochondrial metabolism and insulin signaling in young healthy males. NEW & NOTEWORTHY Short-term (7 day) step reduction reduces the activity of citrate synthase without altering the total or phosphorylated protein content of key markers of skeletal muscle mitochondrial metabolism and insulin signaling in young healthy males.

The benefits of high exogenous glucose availability for endurance exercise performance are well-established. Exogenous glucose oxidation rates are thought to be limited by intestinal glucose transport. Extracellular calcium in rodent intestine increases the translocation of the intestinal glucose transporter GLUT2 which, if translated to humans, could increase the capacity for exogenous glucose availability during exercise. Therefore, this pilot study aimed to explore the effect of calcium co-ingestion during endurance exercise on exogenous glucose oxidation in healthy men. Eight healthy men cycled for 2 h at 50% peak power output, ingesting either 1.2 g min -1 dextrose alone (GLU) or with the addition of 2000 mg calcium (GLU + CAL), in a randomised crossover design. Expired breath samples were collected to determine whole-body and exogenous glucose oxidation. Peak exogenous glucose oxidation during GLU was 0.83 ± 0.15 g min -1 , and was not enhanced during GLU + CAL (0.88 ± 0.11 g min -1 , p  = 0.541). The relative contributions of exogenous carbohydrate (19 ± 3% vs. 20 ± 2%, p  = 0.434), endogenous carbohydrate (65 ± 3% vs. 65 ± 3%, p  = 0.822) and fat (16 ± 3% vs. 15 ± 3%, p  = 0.677) to total substrate utilisation did not differ between trials. These results suggest the addition of calcium to glucose ingestion, at saturating glucose ingestion rates, does not appear to alter exogenous glucose oxidation during endurance exercise in healthy men.

Background: This mixed methods study explored how social media use informed physical activity and diet-related behaviours, and self-perceived Quality of Life (QoL) during COVID-19, and assessed the contextual factors that drive social media use for health-related behaviour change in diverse groups. During the COVID-19 lockdown periods there were reported changes to social media use and health behaviours, and this gave an opportunity to investigate potential relationships., Methods: An explanatory sequential research design of two parts was used: (1) An online survey that assessed social media use in relation to physical activity levels, diet quality and QoL (n = 786; Mage 45.1 ± 19.1 (range 16-88) years; Female =69%); (2) 20 purposive focus groups (n = 69; Mage = 52.88 ± 18.45 years, Female n = 68%) to understand the contextual factors that drive social media use for health-related behaviour change. Descriptive and thematic analysis were conducted., Results: Participants in this study reported that social media facilitated the self-management of behaviours related to physical activity, diet and QoL, through access to information to inform workouts and dietary quality, and the opportunities for interaction with peers, family members and within social groups. Contextual factors including work, home and lifestyle arrangements, pre-existing health-related knowledge and behaviours, and the perceived value of social media for health influenced the relationship between social media use and self-reported outcomes. Social media influencers, peers/family members, and official organisations influenced the application of health-related information accessed via social media., Conclusions: The evidence shows that participants were critical users of social media and were able to use social media to derive benefit for their health and wellbeing. Detailed guidance for those who use social media, as well as those who recommend and endorse social media content is required to maximise the potential of social media to support health behaviours. Future public health strategies and social media interventions should acknowledge diversity in contextual factors driving social media use for health behaviour change.

Altering dietary carbohydrate (CHO) intake modulates fuel utilization during exercise. However, there has been no systematic evaluation of metabolic responses to graded changes in short-term (< 1 wk) dietary CHO intake. Thirteen active men performed interval running exercise combined with isocaloric diets over 3 days before evaluation of metabolic responses to 60-min running at 65% V̇O 2max on three occasions. Diets contained lower [LOW, 2.40 ± 0.66 g CHO·kg -1 ·day -1 , 21.3 ± 0.5% of energy intake (EI)], moderate (MOD, 4.98 ± 1.31 g CHO·kg -1 ·day -1 , 46.3 ± 0.7% EI), or higher (HIGH, 6.48 ± 1.56 g CHO·kg -1 ·day -1 , 60.5 ± 1.6% EI) CHO. Preexercise muscle glycogen content was lower in LOW [54.3 ± 26.4 mmol·kg -1 wet weight (ww)] compared with MOD (82.6 ± 18.8 mmol·kg  -1 ww) and HIGH (80.4 ± 26.0 mmol·kg -1 ww, P < 0.001; MOD vs. HIGH, P = 0.85). Whole body substrate oxidation, systemic responses, and muscle substrate utilization during exercise indicated increased fat and decreased CHO metabolism in LOW [respiratory exchange ratio (RER): 0.81 ± 0.01] compared with MOD (RER 0.86 ± 0.01, P = 0.0005) and HIGH (RER: 0.88 ± 0.01, P < 0.0001; MOD vs. HIGH, P = 0.14). Higher basal muscle expression of genes encoding proteins implicated in fat utilization was observed in LOW. In conclusion, muscle glycogen availability and subsequent metabolic responses to exercise were resistant to increases in dietary CHO intake from ∼5.0 to ∼6.5 g CHO·kg -1 ·day -1 (46% to 61% EI), while muscle glycogen, gene expression, and metabolic responses were sensitive to more marked reductions in CHO intake (∼2.4 g CHO·kg -1 ·day -1 , ∼21% EI). NEW & NOTEWORTHY The data presented here suggest that metabolic responses to steady-state aerobic exercise are somewhat resistant to short-term changes in dietary carbohydrate (CHO) intake within the 5-6.5 g CHO·kg -1 ·day -1 [46-61% energy intake (EI)] range. In contrast, reduction in short-term dietary CHO intake to ∼2.4 g CHO·kg -1 ·day -1 (21% EI) evoked clear changes indicative of increased fat and decreased CHO metabolism during exercise.

Purpose of Review: The present review summarized evidence on the role of carbohydrates in recovery from exercise within the context of acute and chronic effects on metabolism and performance., Recent Findings: Recent studies demonstrate that, in contrast to recovery of muscle glycogen stores, the recovery of liver glycogen stores can be accelerated by the co-ingestion of fructose with glucose-based carbohydrates. Three recent studies suggest this can extend time-to-exhaustion during endurance exercise tests. However, periodically restricting carbohydrate intakes during recovery from some training sessions to slow the recovery of liver and muscle glycogen stores may, over time, result in a modest increase in the ability to oxidize fat during exercise in a fasted state. Whether this periodized strategy translates into a performance advantage in the fed state remains to be clearly demonstrated., Summary: To maximize recovery of glycogen stores and the capacity to perform in subsequent endurance exercise, athletes should consider ingesting at least 1.2 g carbohydrate per kilogram body mass per hour - for the first few hours of recovery - as a mixture of fructose and glucose-based carbohydrates. However, if a goal is increased capacity for fat oxidation, athletes should consider restricting carbohydrate intakes during recovery from some key training sessions., Video Abstract: http://links.lww.com/COCN/A15., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The impact of resistance exercise frequency on muscle protein synthesis rates remains unknown. The aim of this study was to compare daily myofibrillar protein synthesis rates over a 7-day period of low-frequency (LF) versus high-frequency (HF) resistance exercise training. Nine young men (21 ± 2 years) completed a 7-day period of habitual physical activity (BASAL). This was followed by a 7-day exercise period of volume-matched, LF (10 × 10 repetitions at 70% one-repetition maximum, once per week) or HF (2 × 10 repetitions at ∼70% one-repetition maximum, five times per week) resistance exercise training. The participants had one leg randomly allocated to LF and the other to HF. Skeletal muscle biopsies and daily saliva samples were collected to determine myofibrillar protein synthesis rates using 2H2O, with intracellular signaling determined using Western blotting. The myofibrillar protein synthesis rates did not differ between the LF (1.46 ± 0.26%/day) and HF (1.48 ± 0.33%/day) conditions over the 7-day exercise training period (p > .05). There were no significant differences between the LF and HF conditions over the first 2 days (1.45 ± 0.41%/day vs. 1.25 ± 0.46%/day) or last 5 days (1.47 ± 0.30%/day vs. 1.50 ± 0.41%/day) of the exercise training period (p > .05). Daily myofibrillar protein synthesis rates were not different from BASAL at any time point during LF or HF (p > .05). The phosphorylation status and total protein content of selected proteins implicated in skeletal muscle ribosomal biogenesis were not different between conditions (p > .05). Under the conditions of the present study, resistance exercise training frequency did not modulate daily myofibrillar protein synthesis rates in young men.

Endurance athletes are frequently exposed to environmental heat stress during training. We investigated whether exposure to 33°C during training would improve endurance performance in temperate conditions and stimulate mitochondrial adaptations. Seventeen endurance-trained males were randomly assigned to perform a 3-week training intervention in 18°C (TEMP) or 33°C (HEAT). An incremental test and 30-min time-trial preceded by 2-h low-intensity cycling were performed in 18°C pre- and post-intervention, along with a resting vastus lateralis microbiopsy. Training was matched for relative cardiovascular demand using heart rates measured at the first and second ventilatory thresholds, along with a weekly "best-effort" interval session. Perceived training load was similar between-groups, despite lower power outputs during training in HEAT versus TEMP (p < .05). Time-trial performance improved to a greater extent in HEAT than TEMP (30 ± 13 vs. 16 ± 5 W, N = 7 vs. N = 6, p = .04), and citrate synthase activity increased in HEAT (fold-change, 1.25 ± 0.25, p = .03, N = 9) but not TEMP (1.10 ± 0.22, p = .22, N = 7). Training-induced changes in time-trial performance and citrate synthase activity were related (r = .51, p = .04). A group × time interaction for peak fat oxidation was observed (Δ 0.05 ± 0.14 vs. -0.09 ± 0.12 g·min -1 in TEMP and HEAT, N = 9 vs. N = 8, p = .05). Our data suggest exposure to moderate environmental heat stress during endurance training may be useful for inducing adaptations relevant to performance in temperate conditions., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Key Points: Acute nicotinamide riboside (NR) supplementation does not alter substrate metabolism at rest, during or in recovery from endurance exercise. NR does not alter NAD + -sensitive signalling pathways in human skeletal muscle. NR supplementation and acute exercise influence the NAD + metabolome., Abstract: Oral supplementation of the NAD + precursor nicotinamide riboside (NR) has been reported to alter metabolism alongside increasing sirtuin (SIRT) signalling and mitochondrial biogenesis in rodent skeletal muscle. However, whether NR supplementation can elicit a similar response in human skeletal muscle is unclear. This study assessed the effect of 7-day NR supplementation on whole-body metabolism and exercise-induced mitochondrial biogenic signalling in skeletal muscle. Eight male participants (age: 23 ± 4 years, V ̇ O 2 peak 46.5 ± 4.4 ml kg -1  min -1 ) received 1 week of NR or cellulose placebo (PLA) supplementation (1000 mg day -1 ). Muscle biopsies were collected from the medial vastus lateralis prior to supplementation and pre-, immediately post- and 3 h post-exercise (1 h of 60% W max cycling) performed following the supplementation period. There was no effect of NR supplementation on substrate utilisation at rest or during exercise or on skeletal muscle mitochondrial respiration. Global acetylation, auto-PARylation of poly ADP-ribose polymerase 1 (PARP1), acetylation of Tumour protein 53 (p53) Lys382 and Manganese superoxide dismutase (MnSOD) Lys122 were also unaffected by NR supplementation or exercise. NR supplementation did not increase skeletal muscle NAD + concentration, but it did increase the concentration of deaminated NAD + precursors nicotinic acid riboside (NAR) and nicotinic acid mononucleotide (NAM) and methylated nicotinamide breakdown products (Me2PY and Me4PY), demonstrating the skeletal muscle bioavailability of NR supplementation. In summary, 1 week of NR supplementation does not alter whole-body metabolism or skeletal muscle signal transduction pathways implicated in the mitochondrial adaptation to endurance exercise., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)

Training with low carbohydrate availability enhances endurance training adaptations but training volume may be compromised. We explored whole-body metabolism and performance with delayed carbohydrate feeding during exercise undertaken following acute sleep-low training. We hypothesised this strategy would not suppress fat oxidation and would maintain exercise performance. The study involved three experimental trials and included 9 men and 1 woman (⩒O 2 peak = 58.8 ± 5.5 mL kg -1 min -1 ). Each trial started in the afternoon with an exhaustive cycling protocol. The following morning 1-h of steady-state cycling (SS) was followed by a time trial (TT). Carbohydrates (CHO) were not ingested in recovery from exhaustive exercise or during next day exercise in the Placebo trial (PLA); CHO were not ingested during recovery but were fed (15 g every ∼15-min) from 30-min into SS and continued during the TT in the delayed feeding trial (DELAY); CHO were provided during recovery (1.2 g/kg/h for 7 h) and next day exercise (as in DELAY) in a third condition (CHO). Exercise metabolism was assessed using indirect calorimetry and blood sampling. Fat oxidation rates during SS were similar in PLA (0.83 ± 0.17 g/min) and DELAY (0.78 ± 0.14 g/min) ( p  > 0.05) and higher than CHO (0.57 ± 0.27 g/min) ( p  < 0.05). There were no significant differences in TT performance (49.1 ± 10.7, 43.4 ± 7.6, 41.0 ± 7.9 min in PLA, DELAY and CHO, respectively; p  > 0.05). Delayed carbohydrate feeding could be a strategy to maintain high-fat oxidation rates typically associated with exercise undertaken after the sleep-low approach to training but the acute performance effects remain inconclusive.

Purpose: Ingesting readily oxidized carbohydrates (CHO) such as sucrose during exercise can improve endurance performance. Whether lactose can be utilized as a fuel source during exercise is unknown. The purpose of this study was to investigate the metabolic response to lactose ingestion during exercise, compared with sucrose or water., Methods: Eleven participants (age, 22 ± 4 yr; V[Combining Dot Above]O2peak, 50.9 ± 4.7 mL·min·kg) cycled at 50% Wmax for 150 min on five occasions. Participants ingested CHO beverages (lactose or sucrose; 48 g·h, 0.8 g·min) or water throughout exercise. Total substrate and exogenous CHO oxidation was estimated using indirect calorimetry and stable isotope techniques (naturally high C-abundance CHO ingestion). Naturally low C-abundance CHO trials were conducted to correct background shifts in breath CO2 production. Venous blood samples were taken to determine plasma glucose, lactate, and nonesterified fatty acid concentrations., Results: Mean exogenous CHO oxidation rates were comparable with lactose (0.56 ± 0.19 g·min) and sucrose (0.61 ± 0.10 g·min; P = 0.49) ingestion. Endogenous CHO oxidation contributed less to energy expenditure in lactose (38% ± 14%) versus water (50% ± 11%, P = 0.01) and sucrose (50% ± 7%, P ≤ 0.05). Fat oxidation was higher in lactose (42% ± 8%) than in sucrose (28% ± 6%; P ≤ 0.01); CHO conditions were lower than water (50% ± 11%; P ≤ 0.05). Plasma glucose was higher in lactose and sucrose than in water (P ≤ 0.01); plasma lactate was higher in sucrose than in water (P ≤ 0.01); plasma nonesterified fatty acids were higher in water than in sucrose (P ≤ 0.01)., Conclusions: Lactose and sucrose exhibited similar exogenous CHO oxidation rates during exercise at moderate ingestion rates. Compared with sucrose ingestion, lactose resulted in higher fat and lower endogenous CHO oxidation.

Background: Current sports nutrition guidelines recommend athletes ingest carbohydrates at 1.0-1.2 g·kg -1 ·h -1 to optimize repletion of muscle glycogen during short-term recovery from endurance exercise. However, they do not provide specific advice on monosaccharides (e.g., fructose or glucose) other than to ingest carbohydrates of moderate to high glycaemic index. Recent evidence suggests that combined ingestion of fructose and glucose in recovery leads to enhanced liver glycogen synthesis and that this translates into improvement of subsequent endurance capacity. Purpose: The purpose of the present study was to investigate whether consuming a combination of fructose and glucose as opposed to glucose alone during short-term recovery (i.e., 4 h) from exhaustive exercise would also improve subsequent pre-loaded cycle time trial (TT) performance. Methods: Eight participants (seven men, one woman; V ∙ O 2 peak: 56.8 ± 5.0 mLO 2 ·min -1 ·kg -1 ; Wmax: 352 ± 41 W) participated in this randomized double-blind study. Each experimental session involved a glycogen reducing exercise bout in the morning, a 4-h recovery period and 1-h of steady state (SS) exercise at 50% Wmax followed by a ~40-min simulated TT. During recovery carbohydrates were ingested at a rate of 1.2 g·kg -1 ·h -1 in the form of fructose and maltodextrin (FRU + MD) or dextrose and maltodextrin (GLU + MD) (both in 1:1.5 ratio). Substrate oxidation rates, including ingested carbohydrate oxidation, were determined during the steady state (SS). Blood samples were collected during recovery, during the SS exercise and at the end of the TT for determination of glucose and lactate concentrations. Results: There were no differences in TT performance [37.41 ± 3.45 (GLU + MD); 37.96 ± 5.20 min (FRU + MD), p = 0.547]. During the first 45-min of SS oxidation of ingested carbohydrates was greater in FRU + MD (1.86 ± 0.41 g -1 ·min -1 and 1.51 ± 0.37 g -1 ·min -1 for FRU + MD and GLU + MD, respectively; time x condition interaction p = 0.003) and there was a trend toward higher overall carbohydrate oxidation rates in FRU + MD (2.50 ± 0.36 g -1 ·min -1 and 2.31 ± 0.37 g -1 ·min -1 for FRU + MD and GLU + MD, respectively; p = 0.08). However, at 60-min of SS, differences in substrate oxidation disappeared. Conclusion: Ingestion of combined fructose and glucose compared to glucose only during recovery from an exhaustive exercise bout increased the ingested carbohydrate oxidation rate during subsequent exercise. Under the conditions studied, subsequent TT performance was not improved with fructose-glucose., (Copyright © 2020 Podlogar and Wallis.)

Purpose: Maximizing carbohydrate availability is important for many endurance events. Combining pectin and sodium alginate with ingested maltodextrin-fructose (MAL + FRU + PEC + ALG) has been suggested to enhance carbohydrate delivery via hydrogel formation, but the influence on exogenous carbohydrate oxidation remains unknown. The primary aim of this study was to assess the effects of MAL + FRU + PEC + ALG on exogenous carbohydrate oxidation during exercise compared with a maltodextrin-fructose mixture (MAL + FRU). MAL + FRU has been well established to increase exogenous carbohydrate oxidation during cycling compared with glucose-based carbohydrates (MAL + GLU). However, much evidence focuses on cycling, and direct evidence in running is lacking. Therefore, a secondary aim was to compare exogenous carbohydrate oxidation rates with MAL + FRU versus MAL + GLU during running., Methods: Nine trained runners completed two trials (MAL + FRU and MAL + FRU + PEC + ALG) in a double-blind, randomized crossover design. A subset (n = 7) also completed a MAL + GLU trial to address the secondary aim, and a water trial to establish background expired CO2 enrichment. Participants ran at 60% V˙O2peak for 120 min while ingesting either water only or carbohydrate solutions at a rate of 1.5 g carbohydrate per minute., Results: At the end of 120 min of exercise, exogenous carbohydrate oxidation rates were 0.9 (SD 0.5) g·min with MAL + GLU ingestion. MAL + FRU ingestion increased exogenous carbohydrate oxidation rates to 1.1 (SD 0.3) g·min (P = 0.038), with no further increase with MAL + FRU + PEC + ALG ingestion (1.1 (SD 0.3) g·min; P = 1.0). No time-treatment interaction effects were observed for plasma glucose, lactate, insulin, or nonesterified fatty acids, or for ratings of perceived exertion or gastrointestinal symptoms (all, P > 0.05)., Conclusion: To maximize exogenous carbohydrate oxidation during moderate-intensity running, athletes may benefit from consuming glucose(polymer)-fructose mixtures over glucose-based carbohydrates alone, but the addition of pectin and sodium alginate offers no further benefit.

Context: Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness., Objective: To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism., Design: (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study)., Setting: General community., Participants: Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study)., Interventions: Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion., Results: Acute Study-exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: -3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P < 0.01) and type II fibers (-1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P < 0.05). Training Study-postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P > 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs -21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P < 0.05)., Conclusions: Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia., (© Endocrine Society 2019.)

Purpose: Across the lifespan, physical activity levels decrease and time spent sedentary typically increases. However, little is known about the impact that these behavioral changes have on skeletal muscle mass regulation. The primary aim of this study was to use a step reduction model to determine the impact of reduced physical activity and increased sedentary time on daily myofibrillar protein synthesis rates in healthy young men., Methods: Eleven men (22 ± 2 yr) completed 7 d of habitual physical activity (HPA) followed by 7 d of step reduction (SR). Myofibrillar protein synthesis rates were determined during HPA and SR using the deuterated water (H2O) method combined with the collection of skeletal muscle biopsies and daily saliva samples. Gene expression of selected proteins related to muscle mass regulation and oxidative metabolism were determined via real time reverse transcription-quantitative polymerase chain reaction (RT-qPCR)., Results: Daily step count was reduced by approximately 91% during SR (from 13,054 ± 2763 steps per day to 1192 ± 330 steps per day; P < 0.001) and this led to an increased contribution of sedentary time to daily activity (73% ± 6% to 90% ± 3%; P < 0.001). Daily myofibrillar protein synthesis decreased by approximately 27% from 1.39 ± 0.32%·d during HPA to 1.01 ± 0.38%·d during SR (P < 0.05). Muscle atrophy F-box and myostatin mRNA expression were upregulated, whereas mechanistic target of rapamycin, p53, and PDK4 mRNA expression were downregulated after SR (P < 0.05)., Conclusions: One week of reduced physical activity and increased sedentary time substantially lowers daily myofibrillar protein synthesis rates in healthy young men.

Nicotinamide adenine dinucleotide (NAD + ) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD + metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD + metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses., Design: Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period., Results: Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose., Conclusion: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation., Competing Interests: Competing interests: A patent application for ’Compounds and their effects on appetite control and insulin sensitivity' surrounding the use of inulin-propionate ester has been filed by GSF and DJM (WO2014020344). None of the other authors reported a conflict of interest related to the study., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: At rest, omission of breakfast lowers daily energy intake, but also lowers energy expenditure, attenuating any effect on energy balance. The effect of breakfast omission on energy balance when exercise is prescribed is unclear., Objectives: The aim of this study was to assess the effect on 24-h energy balance of omitting compared with consuming breakfast prior to exercise., Methods: Twelve healthy physically active young men (age 23 ± 3 y, body mass index 23.6 ± 2.0 kg/m2) completed 3 trials in a randomized order (separated by >1 week): a breakfast of oats and milk (431 kcal; 65 g carbohydrate, 11 g fat, 19 g protein) followed by rest (BR); breakfast before exercise (BE; 60 min cycling at 50 % peak power output); and overnight fasting before exercise (FE). The 24-h energy intake was calculated based on the food consumed for breakfast, followed by an ad libitum lunch, snacks, and dinner. Indirect calorimetry with heart-rate accelerometry was used to measure substrate utilization and 24-h energy expenditure. A [6,6-2H2]glucose infusion was used to investigate tissue-specific carbohydrate utilization., Results: The 24-h energy balance was -400 kcal (normalized 95% CI: -230, -571 kcal) for the FE trial; this was significantly lower than both the BR trial (492 kcal; normalized 95% CI: 332, 652 kcal) and the BE trial (7 kcal; normalized 95% CI: -153, 177 kcal; both P < 0.01 compared with FE). Plasma glucose utilization in FE (mainly representing liver glucose utilization) was positively correlated with energy intake compensation at lunch (r = 0.62, P = 0.03), suggesting liver carbohydrate plays a role in postexercise energy-balance regulation., Conclusions: Neither exercise energy expenditure nor restricted energy intake via breakfast omission were completely compensated for postexercise. In healthy men, pre-exercise breakfast omission creates a more negative daily energy balance and could therefore be a useful strategy to induce a short-term energy deficit. This trial was registered at clinicaltrials.gov as NCT02258399., (Copyright © American Society for Nutrition 2019.)

Supplementation with inulin-propionate ester (IPE), which delivers propionate to the colon, suppresses ad libitum energy intake and stimulates the release of satiety hormones acutely in humans, and prevents weight gain. In order to determine whether IPE remains effective when incorporated into food products (FP), IPE needs to be added to a widely accepted food system. A bread roll and fruit smoothie were produced. Twenty-one healthy overweight and obese humans participated. Participants attended an acclimatisation visit and a control visit where they consumed un-supplemented food products (FP). Participants then consumed supplemented-FP, containing 10 g/d inulin or IPE for six days followed by a post-supplementation visit in a randomised crossover design. On study visits, supplemented-FP were consumed for the seventh time and ad libitum energy intake was assessed 420 min later. Blood samples were collected to assess hormones and metabolites. Resting energy expenditure (REE) was measured using indirect calorimetry. Taste and appearance ratings were similar between FP. Ad libitum energy intake was significantly different between treatments, due to a decreased intake following IPE-FP. These observations were not related to changes in blood hormones and metabolites. There was an increase in REE following IPE-FP. However, this effect was lost after correcting for changes in fat free mass. Our results suggest that IPE suppresses appetite and may alter REE following its incorporation into palatable food products.

Background: Rejection with severe hemodynamic compromise (RSHC) carries a mortality risk approaching 50%. We aimed to identify current risk factors for RSHC and predictors of graft failure after RSHC., Methods: Data from 3,259 heart transplant (HT) recipients between January 2005 and December 2015 in the Pediatric Heart Transplant Study (PHTS) were analyzed. Predictors for RSHC and outcome after RSHC were sought. Time to RSHC was analyzed using the Cox proportional hazards regression model. Cardiac allograft vasculopathy (CAV) after HT and CAV after RSHC were analyzed as time-dependent covariates. Timing of RSHC was analyzed as occurring before and after 4 years after RSHC., Results: There were 309 patients (9.5%) with ≥ 1 RSHC episodes. In 143 patients with RSHC, the first episode was within 1 year after HT. Independent risk factors for RSHC were age 1 to 5 years at HT (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.04-2.18), age > 10 years at HT (HR, 1.83; 95% CI, 1.29-2.60), black race (HR, 1.64; 95% CI, 1.25-2.15), prior cardiac surgery (HR, 1.55; 95% CI, 1.03-2.31), ventricular assist device support at HT (HR, 1.65; 95% CI, 1.18-2.29), maintenance steroids (HR, 1.39; 95% CI, 1.06-1.82), and recipient on inotropes, pressors, or thyroid hormones (HR, 1.45; 95% CI, 1.09-1.94). Graft survival at 5 years after RSHC was 45.7%. RSHC was a greater risk factor for earlier CAV (HR, 7.78; 95% CI, 5.82-10.40) than other rejection types (HR, 2.31; 95% CI, 1.79-3.00). Patients with late RSHC, after 1 year after RSHC had increased risk of graft loss 4 years after RSHC (HR, 7.12; 95% CI, 2.18-23.22). The 5-year graft survival after RSHC was 50.5% for early RSHC and 39.0% for late RSHC., Conclusions: Mortality after RSHC is high in the current treatment era. Many patient risk factors for RSHC cannot be modified, including age, race, prior cardiac surgery, and ventricular assist device support. After RSHC, CAV is the only predictor of graft failure. Patients who have late RSHC fare worse than those who have RSHC within the first year after HT., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The objective of this review paper is to evaluate the impact of undertaking aerobic exercise in the overnight-fasted v. fed-state, in the context of optimising the health benefits of regular physical activity. Conducting a single bout of aerobic exercise in the overnight-fasted v. fed-state can differentially modulate the aspects of metabolism and energy balance behaviours. This includes, but is not limited to, increased utilisation of fat as a fuel source, improved plasma lipid profiles, enhanced activation of molecular signalling pathways related to fuel metabolism in skeletal muscle and adipose tissue, and reductions in energy intake over the course of a day. The impact of a single bout of overnight-fasted v. fed-state exercise on short-term glycaemic control is variable, being affected by the experimental conditions, the time frame of measurement and possibly the subject population studied. The health response to undertaking overnight-fasted v. fed-state exercise for a sustained period of time in the form of exercise training is less clear, due to a limited number of studies. From the extant literature, there is evidence that overnight-fasted exercise in young, healthy men can enhance training-induced adaptations in skeletal muscle metabolic profile, and mitigate against the negative consequences of short-term excess energy intake on glucose tolerance compared with exercising in the fed-state. Nonetheless, further long-term studies are required, particularly in populations at-risk or living with cardio-metabolic disease to elucidate if feeding status prior to exercise modulates metabolism or energy balance behaviours to an extent that could impact upon the health or therapeutic benefits of exercise.

The aim of this study was to characterize postprandial glucose flux after exercise in the fed versus overnight fasted state and to investigate the potential underlying mechanisms. In a randomized order, twelve men underwent breakfast-rest [(BR) 3 h semirecumbent], breakfast-exercise [(BE) 2 h semirecumbent before 60 min of cycling (50% peak power output)], and overnight fasted exercise [(FE) as per BE omitting breakfast] trials. An oral glucose tolerance test (OGTT) was completed after exercise (after rest on BR). Dual stable isotope tracers ([U- 13 C] glucose ingestion and [6,6- 2 H 2 ] glucose infusion) and muscle biopsies were combined to assess postprandial plasma glucose kinetics and intramuscular signaling, respectively. Plasma intestinal fatty acid binding (I-FABP) concentrations were determined as a marker of intestinal damage. Breakfast before exercise increased postexercise plasma glucose disposal rates during the OGTT, from 44 g/120 min in FE {35 to 53 g/120 min [mean (normalized 95% confidence interval)] to 73 g/120 min in BE [55 to 90 g/120 min; P = 0.01]}. This higher plasma glucose disposal rate was, however, offset by increased plasma glucose appearance rates (principally OGTT-derived), resulting in a glycemic response that did not differ between BE and FE ( P = 0.11). Plasma I-FABP concentrations during exercise were 264 pg/ml (196 to 332 pg/ml) lower in BE versus FE ( P = 0.01). Breakfast before exercise increases postexercise postprandial plasma glucose disposal, which is offset (primarily) by increased appearance rates of orally ingested glucose. Therefore, metabolic responses to fed-state exercise cannot be readily inferred from studies conducted in a fasted state.

Purpose: Restoring skeletal muscle and hepatic glycogen content during short-term (<6 h) recovery from prolonged exercise is pertinent for athletes seeking to maximize performance in repeated exercise bouts. Previous research suggests that coingestion of fructose-glucose carbohydrate sources augments hepatic and has equivalent effects on skeletal muscle glycogen storage during short-term recovery from prolonged exercise compared with isocaloric glucose ingestion. The aim of the present investigation was to determine whether this has a discernible effect on subsequent exercise capacity., Methods: Eight trained endurance runners and triathletes performed two experimental trials in a single-blind, randomized, and counterbalanced crossover design. Trials involved treadmill running to exhaustion at 70% V˙O2max, a 4-h recovery with 90 g·h of glucose-maltodextrin (GLU + MAL) or fructose-maltodextrin (FRU + MAL) ingestion (1:1.5 ratio), and a second bout of treadmill running to exhaustion at 70% V˙O2max., Results: Exercise capacity in bout 2 was significantly greater with FRU + MAL (81.4 ± 22.3 vs 61.4 ± 9.6 min, P = 0.02), a large magnitude effect (effect size = 1.84 ± 1.12, 32.4% ± 19.9%). Total carbohydrate oxidation rates were not significantly different during bout 1 or 2 between trials, although total carbohydrate oxidized in bout 2 was significantly greater with FRU + MAL (223 ± 66 vs 157 ± 26 g, P = 0.02). Ingested carbohydrate oxidation rates were greater during bout 2 with FRU + MAL (P = 0.001). Plasma glucose and nonesterified fatty acid concentrations were not significantly different between trials. Plasma lactate concentrations were significantly greater during recovery before bout 2 with FRU + MAL (P = 0.001). Self-reported nausea and stomach fullness during bout 2 were marginally in favor of FRU + MAL., Conclusion: Short-term recovery of endurance capacity was significantly enhanced with FRU + MAL versus GLU + MAL ingestion during recovery.

Carbohydrate (CHO) ingestion during exercise lasting less than three hours improves endurance exercise performance but there is still debate about the optimal dose. We utilised stable isotopes and blood metabolite profiles to further examine metabolic responses to CHO (glucose only) ingestion in the 20-64 g·h -1 range, and to determine the association with performance outcome. In a double-blind, randomized cross-over design, male cyclists ( n = 20, mean ± SD, age 34 ± 10 years, mass 75.8 ± 9 kg, peak power output 394 ± 36 W, VO 2max 62 ± 9 mL·kg -1 ·min -1 ) completed four main experimental trials. Each trial involved a two-hour constant load ride (185 ± 25 W) followed by a time trial, where one of three CHO beverages, or a control (water), were administered every 15 min, providing 0, 20, 39 or 64 g CHO·h -1 . Dual glucose tracer techniques, indirect calorimetry and blood analyses were used to determine glucose kinetics, exogenous CHO oxidation (EXO), endogenous CHO and fat oxidation; and metabolite responses. Regression analysis revealed that total exogenous CHO oxidised in the second hour of exercise, and suppression of serum NEFA concentration provided the best prediction model of performance outcome. However, the model could only explain ~19% of the variance in performance outcome. The present data demonstrate that consuming ~40 g·h -1 of CHO appears to be the minimum ingestion rate required to induce metabolic effects that are sufficient to impact upon performance outcome. These data highlight a lack of performance benefit and few changes in metabolic outcomes beyond an ingestion rate of 39 g·h -1 . Further work is required to explore dose-response effects of CHO feeding and associations between multiple metabolic parameters and subsequent performance outcome., Competing Interests: The authors declare no conflict of interest. The founding sponsors had some input into the design of the study, but were not involved in the collection, analyses, or interpretation of data; or in the writing of the manuscript, and in the decision to publish the results.

The ingestion of intact protein or essential amino acids (EAA) stimulates mechanistic target of rapamycin complex-1 (mTORC1) signaling and muscle protein synthesis (MPS) following resistance exercise. The purpose of this study was to investigate the response of myofibrillar-MPS to ingestion of branched-chain amino acids (BCAAs) only (i.e., without concurrent ingestion of other EAA, intact protein, or other macronutrients) following resistance exercise in humans. Ten young (20.1 ± 1.3 years), resistance-trained men completed two trials, ingesting either 5.6 g BCAA or a placebo (PLA) drink immediately after resistance exercise. Myofibrillar-MPS was measured during exercise recovery with a primed, constant infusion of L-[ring 13 C 6 ] phenylalanine and collection of muscle biopsies pre and 4 h-post drink ingestion. Blood samples were collected at time-points before and after drink ingestion. Western blotting was used to measure the phosphorylation status of mTORC1 signaling proteins in biopsies collected pre, 1-, and 4 h-post drink. The percentage increase from baseline in plasma leucine (300 ± 96%), isoleucine (300 ± 88%), and valine (144 ± 59%) concentrations peaked 0.5 h-post drink in BCAA. A greater phosphorylation status of S6K1 Thr389 ( P = 0.017) and PRAS40 ( P = 0.037) was observed in BCAA than PLA at 1 h-post drink ingestion. Myofibrillar-MPS was 22% higher ( P = 0.012) in BCAA (0.110 ± 0.009%/h) than PLA (0.090 ± 0.006%/h). Phenylalanine Ra was ~6% lower in BCAA (18.00 ± 4.31 μmol·kgBM -1 ) than PLA (21.75 ± 4.89 μmol·kgBM -1 ; P = 0.028) after drink ingestion. We conclude that ingesting BCAAs alone increases the post-exercise stimulation of myofibrillar-MPS and phosphorylation status mTORC1 signaling.

Background: Substantial interindividual variability exists in the maximal rate of fat oxidation (MFO) during exercise with potential implications for metabolic health. Although the diet can affect the metabolic response to exercise, the contribution of a self-selected diet to the interindividual variability in the MFO requires further clarification. Objective: We sought to identify whether recent, self-selected dietary intake independently predicts the MFO in healthy men and women. Design: The MFO and maximal oxygen uptake ([Formula: see text]O 2 max) were determined with the use of indirect calorimetry in 305 healthy volunteers [150 men and 155 women; mean ± SD age: 25 ± 6 y; body mass index (BMI; in kg/m 2 ): 23 ± 2]. Dual-energy X-ray absorptiometry was used to assess body composition with the self-reported physical activity level (SRPAL) and dietary intake determined in the 4 d before exercise testing. To minimize potential confounding with typically observed sex-related differences (e.g., body composition), predictor variables were mean-centered by sex. In the analyses, hierarchical multiple linear regressions were used to quantify each variable's influence on the MFO. Results: The mean absolute MFO was 0.55 ± 0.19 g/min (range: 0.19-1.13 g/min). A total of 44.4% of the interindividual variability in the MFO was explained by the [Formula: see text]O 2 max, sex, and SRPAL with dietary carbohydrate (carbohydrate; negative association with the MFO) and fat intake (positive association) associated with an additional 3.2% of the variance. When expressed relative to fat-free mass (FFM), the MFO was 10.8 ± 3.2 mg · kg FFM -1 · min -1 (range: 3.5-20.7 mg · kg FFM -1 · min -1 ) with 16.6% of the variability explained by the [Formula: see text]O 2 max, sex, and SRPAL; dietary carbohydrate and fat intakes together explained an additional 2.6% of the variability. Biological sex was an independent determinant of the MFO with women showing a higher MFO [men: 10.3 ± 3.1 mg · kg FFM -1 · min -1 (3.5-19.9 mg · kg FFM -1 · min -1 ); women: 11.2 ± 3.3 mg · kg FFM -1 · min -1 (4.6-20.7 mg · kg FFM -1 · min -1 ); P < 0.05]. Conclusion: Considered alongside other robust determinants, dietary carbohydrate and fat intake make modest but independent contributions to the interindividual variability in the capacity to oxidize fat during exercise. This trial was registered at clinicaltrials.gov as NCT02070055.

Aims: Diet-derived short chain fatty acids (SCFAs) improve glucose homeostasis in vivo, but the role of individual SCFAs and their mechanisms of action have not been defined. This study evaluated the effects of increasing colonic delivery of the SCFA propionate on β-cell function in humans and the direct effects of propionate on isolated human islets in vitro., Materials and Methods: For 24 weeks human subjects ingested an inulin-propionate ester that delivers propionate to the colon. Acute insulin, GLP-1 and non-esterified fatty acid (NEFA) levels were quantified pre- and post-supplementation in response to a mixed meal test. Expression of the SCFA receptor FFAR2 in human islets was determined by western blotting and immunohistochemistry. Dynamic insulin secretion from perifused human islets was quantified by radioimmunoassay and islet apoptosis was determined by quantification of caspase 3/7 activities., Results: Colonic propionate delivery in vivo was associated with improved β-cell function with increased insulin secretion that was independent of changes in GLP-1 levels. Human islet β-cells expressed FFAR2 and propionate potentiated dynamic glucose-stimulated insulin secretion in vitro, an effect that was dependent on signalling via protein kinase C. Propionate also protected human islets from apoptosis induced by the NEFA sodium palmitate and inflammatory cytokines., Conclusions: Our results indicate that propionate has beneficial effects on β-cell function in vivo, and in vitro analyses demonstrated that it has direct effects to potentiate glucose-stimulated insulin release and maintain β-cell mass through inhibition of apoptosis. These observations support ingestion of propiogenic dietary fibres to maintain healthy glucose homeostasis., (© 2016 John Wiley & Sons Ltd.)

Background: For unknown reasons, interval training often reduces body weight more than energy-expenditure matched continuous training. We compared the acute effects of time-duration and oxygen-consumption matched interval- vs. continuous exercise on excess post-exercise oxygen consumption (EPOC), substrate oxidation rates and lipid metabolism in the hours following exercise in subjects with type 2 diabetes (T2D)., Methods: Following an overnight fast, ten T2D subjects (M/F: 7/3; age=60.3±2.3years; body mass index (BMI)=28.3±1.1kg/m(2)) completed three 60-min interventions in a counterbalanced, randomized order: 1) control (CON), 2) continuous walking (CW), 3) interval-walking (IW - repeated cycles of 3min of fast and 3min of slow walking). Indirect calorimetry was applied during each intervention and repeatedly for 30min per hour during the following 5h. A liquid mixed meal tolerance test (MMTT, 450kcal) was consumed by the subjects 45min after completion of the intervention with blood samples taken regularly., Results: Exercise interventions were successfully matched for total oxygen consumption (CW=1641±133mL/min; IW=1634±126mL/min, P>0.05). EPOC was higher after IW (8.4±1.3l) compared to CW (3.7±1.4l, P<0.05). Lipid oxidation rates were increased during the MMTT in IW (1.03±0.12mg/kg per min) and CW (0.87±0.04mg/kg per min) compared with CON (0.73±0.04mg/kg per min, P<0.01 and P<0.05, respectively), with no difference between IW and CW. Moreover, free fatty acids and glycerol concentrations, and glycerol kinetics were increased comparably during and after IW and CW compared to CON., Conclusions: Interval exercise results in greater EPOC than oxygen-consumption matched continuous exercise during a post-exercise MMTT in subjects with T2D, whereas effects on substrate oxidation and lipid metabolism are comparable., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The currently accepted amount of protein required to achieve maximal stimulation of myofibrillar protein synthesis (MPS) following resistance exercise is 20-25 g. However, the influence of lean body mass (LBM) on the response of MPS to protein ingestion is unclear. Our aim was to assess the influence of LBM, both total and the amount activated during exercise, on the maximal response of MPS to ingestion of 20 or 40 g of whey protein following a bout of whole-body resistance exercise. Resistance-trained males were assigned to a group with lower LBM (≤65 kg; LLBM n = 15) or higher LBM (≥70 kg; HLBM n = 15) and participated in two trials in random order. MPS was measured with the infusion of (13)C6-phenylalanine tracer and collection of muscle biopsies following ingestion of either 20 or 40 g protein during recovery from a single bout of whole-body resistance exercise. A similar response of MPS during exercise recovery was observed between LBM groups following protein ingestion (20 g - LLBM: 0.048 ± 0.018%·h(-1); HLBM: 0.051 ± 0.014%·h(-1); 40 g - LLBM: 0.059 ± 0.021%·h(-1); HLBM: 0.059 ± 0.012%·h(-1)). Overall (groups combined), MPS was stimulated to a greater extent following ingestion of 40 g (0.059 ± 0.020%·h(-1)) compared with 20 g (0.049 ± 0.020%·h(-1); P = 0.005) of protein. Our data indicate that ingestion of 40 g whey protein following whole-body resistance exercise stimulates a greater MPS response than 20 g in young resistance-trained men. However, with the current doses, the total amount of LBM does not seem to influence the response., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

The maximal capacity to oxidize fat during exercise (MFO) is associated with 24-h fat balance and insulin sensitivity. Understanding factors that influence MFO could have implications for metabolic health. We investigated relationships between selected plasma metabolites, hormones and overnight-fasted resting fat oxidation rates (Resting), with MFO. Resting fat oxidation and MFO was measured in 57 men with blood collected at rest and during exercise. Plasma glycerol (R=0.39, P=0.033), non-esterified fatty acids (NEFA: R=0.27, P=0.030) and insulin (R=- 0.36, P=0.007) measured at MFO correlated with MFO; only glycerol remained correlated when controlled for resting concentrations (R=0.36, P=0.008). The change in glycerol from rest to MFO correlated with exercise-induced fat oxidation (R=0.32, P=0.012). V˙O 2max correlated with resting fat oxidation (R=0.44, P=0.001) and MFO (R=0.52, P<0.001). Resting fat oxidation correlated with MFO (R=0.55, P<0.001); this remained when controlled for V˙O 2max (R=0.41, P=0.001). This study reports weak-to-moderate, albeit significant, relationships between plasma lipolytic markers, insulin and resting overnight-fasted fat oxidation with MFO and shows the plasma glycerol response to uniquely reflect exercise-induced fat oxidation. V˙O 2max correlates with fat oxidation but the relationship can be dissociated. Interventions to increase fat oxidation for optimal metabolic health would benefit from, but are not reliant on, increases in V˙O 2max., (© Georg Thieme Verlag KG Stuttgart · New York.)

Joint formation begins with the establishment of an interzone within the cartilaginous anlagen of the future skeleton. Both GDF5 and ERG are proposed as regulators of chondrocyte differentiation during and post interzone formation. The aim of this study was to examine the relationship between Gdf5 and Erg expression and downstream effects on chondrocyte gene expression. Erg expression was identified in mouse knee joints at E13.5. Expression analyses were performed using micromass cultures of murine C3H10T1/2 mesenchymal cells undergoing induced chondrogenesis in the presence and absence of GDF5 and ERG. At E13.5, Erg expression was found to surround epiphyseal chondrocytes and span the interzone up to the intermediate zone. Erg splice forms were expressed in micromass cultures, and their expression profile was altered by the addition of recombinant GDF5 depending on the stage of differentiation. Overexpression of Erg-010 resulted in a downregulation of Col2a1 and Col10a1. Microarray analysis following Erg-010 overexpression identified two potential downstream targets, Ube2b and Osr2, which were also differentially regulated by GDF5. Erg regulation by GDF5 in induced mesenchymal cells in vitro is dependent on the stage of chondrogenesis, and its expression in vivo demarcates chondrocytes that are not destined to be consumed by endochondral ossification. Functionally, Erg expression causes downregulation of Col2a1 and Col10a1 expression and this effect is potentially mediated by Osr2 and/or Ube2b. Combined, these data suggest a possible pathway linking GDF5, ERG and downstream factors in the processes of chondrocyte differentiation during articular joint formation.

Background: Beukes hip dysplasia (BHD) is an autosomal dominant disorder of variable penetrance that was originally identified in a large South African family of European origin. BHD is characterised by bilateral dysmorphism of the proximal femur, which results in severe degenerative osteoarthropathy. Previous studies mapped the disorder to a 3.34 Mb region on chromosome 4q35., Objective: To fine-map the BHD locus and identify the disease-causing mutation by direct sequencing., Results: The linked BHD allele was refined to 1.33 Mb, reducing the number of candidate genes from 25 to 16. Analysis of protein coding and invariant splice-site sequences in three distantly related individuals identified a single-candidate disease-causing variant c.868T>C within exon 8 of the ubiquitin-fold modifier 1 (Ufm1)-specific peptidase 2 gene, UFSP2. The presence of this unique mutation was confirmed in all 17 affected members of the BHD family who were genotyped. The mutation segregated with the BHD phenotype in the extended family with a two-point (single marker) LOD score of 10.4 (θ=0.0 and 80% penetrance). The mutation predicts the substitution of a highly conserved amino acid, p.Tyr290His, in the encoded protein. In vitro functional assays performed using purified recombinant wild-type and mutant UFSP2 protein demonstrated that the BHD mutation abolishes UFSP2-mediated C-terminal cleavage of its substrate, Ufm1., Conclusion: We report a unique UFSP2 mutation that segregates with the BHD phenotype. The predicted amino acid substitution inactivates UFSP2 proteolytic function, thus implicating the ubiquitin-fold modifier 1 cascade in this form of severe hip osteoarthropathy. The facile polymerase chain reaction-based assay we describe could be used to confirm the diagnosis of BHD, or for presymptomatic testing of members of the extended BHD family.

Disturbances in fat oxidation have been associated with an increased risk of obesity and metabolic disorders such as insulin resistance. There is large intersubject variability in the capacity to oxidize fat when a person is physically active, although the significance of this for metabolic health is unclear. We investigated whether the maximal capacity to oxidize fat during exercise is related to 24-h fat oxidation and insulin sensitivity. Maximal fat oxidation (MFO; indirect calorimetry during incremental exercise) and insulin sensitivity (Quantitative Insulin Sensitivity Check Index) were measured in 53 young, healthy men (age 24 ± 7 yr, V̇o2max 52 ± 6 ml·kg(-1)·min(-1)). Fat oxidation over 24 h (24-h FO; indirect calorimetry) was assessed in 16 young, healthy men (age 26 ± 8 yr, V̇o2max 52 ± 6 ml·kg(-1)·min(-1)) during a 36-h stay in a whole-room respiration chamber. MFO (g/min) was positively correlated with 24-h FO (g/day) (R = 0.65, P = 0.003; R = 0.46, P = 0.041 when controlled for V̇o2max [l/min]), 24-h percent energy from FO (R = 0.58, P = 0.009), and insulin sensitivity (R = 0.33, P = 0.007). MFO (g/min) was negatively correlated with 24-h fat balance (g/day) (R = -0.51, P = 0.021) but not significantly correlated with 24-h respiratory quotient (R = -0.29, P = 0.142). Although additional investigations are needed, our data showing positive associations between MFO and 24-h FO, and between MFO and insulin sensitivity in healthy young men suggests that a high capacity to oxidize fat while one is physically active could be advantageous for the maintenance of metabolic health., (Copyright © 2015 the American Physiological Society.)

Insulin- and contraction-stimulated increases in glucose uptake into skeletal muscle occur in part as a result of the translocation of glucose transporter 4 (GLUT4) from intracellular stores to the plasma membrane (PM). This study aimed to use immunofluorescence microscopy in human skeletal muscle to quantify GLUT4 redistribution from intracellular stores to the PM in response to glucose feeding and exercise. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of ten insulin-sensitive men in the basal state and following 30 min of cycling exercise (65% VO2 max). Muscle biopsy samples were also taken from a second cohort of ten age-, BMI- and VO2 max-matched insulin-sensitive men in the basal state and 30 and 60 min following glucose feeding (75 g glucose). GLUT4 and dystrophin colocalization, measured using the Pearson's correlation coefficient, was increased following 30 min of cycling exercise (baseline r = 0.47 ± 0.01; post exercise r = 0.58 ± 0.02; P < 0.001) and 30 min after glucose ingestion (baseline r = 0.42 ± 0.02; 30 min r = 0.46 ± 0.02; P < 0.05). Large and small GLUT4 clusters were partially depleted following 30 min cycling exercise, but not 30 min after glucose feeding. This study has, for the first time, used immunofluorescence microscopy in human skeletal muscle to quantify increases in GLUT4 and dystrophin colocalization and depletion of GLUT4 from large and smaller clusters as evidence of net GLUT4 translocation to the PM., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Objective: To test whether previously reported hip morphology or osteoarthritis (OA) susceptibility loci are associated with proximal femur shape as represented by statistical shape model (SSM) modes and as univariate or multivariate quantitative traits., Methods: We used pelvic radiographs and genotype data from 929 subjects with unilateral hip OA who had been recruited previously for the Arthritis Research UK Osteoarthritis Genetics Consortium genome-wide association study. We built 3 SSMs capturing the shape variation of the OA-unaffected proximal femur in the entire mixed-sex cohort and for male/female-stratified cohorts. We selected 41 candidate single-nucleotide polymorphisms (SNPs) previously reported as being associated with hip morphology (for replication analysis) or OA (for discovery analysis) and for which genotype data were available. We performed 2 types of analysis for genotype-phenotype associations between these SNPs and the modes of the SSMs: 1) a univariate analysis using individual SSM modes and 2) a multivariate analysis using combinations of SSM modes., Results: The univariate analysis identified association between rs4836732 (within the ASTN2 gene) and mode 5 of the female SSM (P = 0.0016) and between rs6976 (within the GLT8D1 gene) and mode 7 of the mixed-sex SSM (P = 0.0003). The multivariate analysis identified association between rs5009270 (near the IFRD1 gene) and a combination of modes 3, 4, and 9 of the mixed-sex SSM (P = 0.0004). Evidence of associations remained significant following adjustment for multiple testing. All 3 SNPs had previously been associated with hip OA., Conclusion: These de novo findings suggest that rs4836732, rs6976, and rs5009270 may contribute to hip OA susceptibility by altering proximal femur shape., (© 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.)