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Purpose: The aim of this study was to investigate the influence of manipulating hypoxic severity with low-intensity exercise on glucose regulation in healthy overweight adults.Methods: In a randomized crossover design, 14 males with overweight (age: 27 ± 5 years; body mass index (BMI) 27.1 ± 1.8 kg⋅m2) completed three exercise trials involving 60 min aerobic exercise cycling at 90% lactate threshold in normoxia (NM, FiO2 = 20.9%), moderate hypoxia (MH, FiO2 = 16.5%) and high hypoxia (HH, FiO2 = 14.8%). A post-exercise oral glucose tolerance test (OGTT) was performed. Venous blood samples were analyzed for incremental area under the curve (iAUC), plasma glucose and insulin, as well as exerkine concentrations (plasma apelin and fibroblast growth factor 21 [FGF-21]) pre- and post-exercise. A 24-h continuous glucose monitoring (CGM) was used to determine interstitial glucose concentrations. Heart rate, oxygen saturation (SpO2) and perceptual measures were recorded during exercise.Results: Post-exercise OGTT iAUC for plasma glucose and insulin concentrations were lower in MH vs. control (p = 0.02). Post-exercise interstitial glucose iAUC, plasma apelin and FGF-21 were not different between conditions. Heart rate was higher in HH vs. NM and MH, and MH vs. NM (p < 0.001), while SpO2 was lower in HH vs. NM and MH, and MH vs. NM (p < 0.001). Overall perceived discomfort and leg discomfort were higher in HH vs. NM and MH (p < 0.05), while perceived breathing difficulty was higher in HH vs. NM only (p = 0.003).Conclusion: Compared to higher hypoxic conditions, performing acute aerobic-based exercise under moderate hypoxia provided a more effective stimulus for improving post-exercise glucose regulation while concomitantly preventing excessive physiological and perceptual stress in healthy overweight adults.

We investigated the effect of a high-fat diet (HFD) on serum lipid subfractions in men with overweight/obesity and determined whether morning or evening exercise affected these lipid profiles. In a three-armed randomised trial, 24 men consumed an HFD for 11 days. One group of participants did not exercise (n = 8, CONTROL), one group trained at 06:30 h (n = 8, EXam), and one group at 18:30 h (n = 8, EXpm) on days 6–10. We assessed the effects of HFD and exercise training on circulating lipoprotein subclass profiles using NMR spectroscopy. Five days of HFD induced substantial perturbations in fasting lipid subfraction profiles, with changes in 31/100 subfraction variables (adjusted p values [q] 20% of fasting lipid subfractions. EXpm reduced fasting cholesterol concentrations in three LDL subfractions by ⁓30%, while EXam only reduced concentration in the largest LDL particles by 19% (all q

Purpose of review Time-restricted eating (TRE) entails consuming energy intake within a 4- to 10-h window, with the remaining time spent fasting. Although studies have reported health benefits from TRE, little is known about the impact of TRE on common chronic diseases such as type 2 diabetes, cancer and cardiovascular disease. This review summarizes and critically evaluates the most recent TRE research findings relevant to managing and treating these chronic diseases. Recent findings Most recent TRE studies have been in populations with overweight/obesity or metabolic syndrome; two have been in populations with diabetes, three in cancer survivors and none in populations with cardiovascular disease. Collectively, these studies showed that participants could adhere to TRE and TRE is well tolerated. These studies also showed preliminary efficacy for improved glucose regulation and insulin sensitivity, a reduction in body fat and blood pressure, reduced cardiovascular risk scores and increased quality of life. More research is required to define the most effective TRE protocol (i.e. length and timing of eating window, intervention duration). Summary TRE has demonstrated benefits on cardiovascular, metabolic and clinical outcomes relevant to the underlying pathophysiology, but there are limited data on TRE implemented specifically within populations with diabetes, cancer or cardiovascular disease.

Aims/hypothesis We determined whether the time of day of exercise training (morning vs evening) would modulate the effects of consumption of a high-fat diet (HFD) on glycaemic control, whole-body health markers and serum metabolomics. Methods In this three-armed parallel-group randomised trial undertaken at a university in Melbourne, Australia, overweight/obese men consumed an HFD (65% of energy from fat) for 11 consecutive days. Participants were recruited via social media and community advertisements. Eligibility criteria for participation were male sex, age 30–45 years, BMI 27.0–35.0 kg/m2 and sedentary lifestyle. The main exclusion criteria were known CVD or type 2 diabetes, taking prescription medications, and shift-work. After 5 days, participants were allocated using a computer random generator to either exercise in the morning (06:30 hours), exercise in the evening (18:30 hours) or no exercise for the subsequent 5 days. Participants and researchers were not blinded to group assignment. Changes in serum metabolites, circulating lipids, cardiorespiratory fitness, BP, and glycaemic control (from continuous glucose monitoring) were compared between groups. Results Twenty-five participants were randomised (morning exercise n = 9; evening exercise n = 8; no exercise n = 8) and 24 participants completed the study and were included in analyses (n = 8 per group). Five days of HFD induced marked perturbations in serum metabolites related to lipid and amino acid metabolism. Exercise training had a smaller impact than the HFD on changes in circulating metabolites, and only exercise undertaken in the evening was able to partly reverse some of the HFD-induced changes in metabolomic profiles. Twenty-four-hour glucose concentrations were lower after 5 days of HFD compared with the participants’ habitual diet (5.3 ± 0.4 vs 5.6 ± 0.4 mmol/l, p = 0.001). There were no significant changes in 24 h glucose concentrations for either exercise group but lower nocturnal glucose levels were observed in participants who trained in the evening, compared with when they consumed the HFD alone (4.9 ± 0.4 vs 5.3 ± 0.3 mmol/l, p = 0.04). Compared with the no-exercise group, peak oxygen uptake improved after both morning (estimated effect 1.3 ml min−1 kg−1 [95% CI 0.5, 2.0], p = 0.003) and evening exercise (estimated effect 1.4 ml min−1 kg−1 [95% CI 0.6, 2.2], p = 0.001). Fasting blood glucose, insulin, cholesterol, triacylglycerol and LDL-cholesterol concentrations decreased only in participants allocated to evening exercise training. There were no unintended or adverse effects. Conclusions/interpretation A short-term HFD in overweight/obese men induced substantial alterations in lipid- and amino acid-related serum metabolites. Improvements in cardiorespiratory fitness were similar regardless of the time of day of exercise training. However, improvements in glycaemic control and partial reversal of HFD-induced changes in metabolic profiles were only observed when participants exercise trained in the evening. Trial registration anzctr.org.au registration no. ACTRN12617000304336. Funding This study was funded by the Novo Nordisk Foundation (NNF14OC0011493). Graphical abstract

Introduction Whether short-term, single-mode exercise training can improve physical fitness before a period of reduced physical activity (e.g., postsurgery recovery) is not well characterized in clinical populations or middle-age adults. We investigated skeletal muscle adaptive responses after endurance exercise training (ENT), high-intensity interval training (HIIT), or resistance exercise training (RET), and a subsequent period of detraining, in sedentary, middle-age men. Methods Thirty-five sedentary men (39 +/- 3 yr) were randomized to parallel groups and undertook 6 wk of either ENT (n = 12), HIIT (n = 12), or RET (n = 11) followed by 2.5 wk of detraining. Skeletal muscle fiber characteristics, body composition, muscle thickness, muscle strength, aerobic capacity, resting energy expenditure, and glucose homeostasis were assessed at baseline, and after exercise training and detraining. Results Lean mass increased after RET and HIIT (+3.2% +/- 1.6% and +1.6% +/- 2.1%, P < 0.05). Muscle strength (sum of leg press, leg extension, and bench press one-repetition maximums) increased after all training interventions (RET, +25% +/- 5%; HIIT, +10% +/- 5%; ENT, +7% +/- 7%; P < 0.05). Aerobic capacity increased only after HIIT and ENT (+14% +/- 7% and +11% +/- 11%, P < 0.05). Type I and II muscle fiber size increased for all groups after training (main effect of time, P < 0.05). After a period of detraining, the gains in lean mass and maximal muscle strength were maintained in the RET and HIIT groups, but maximal aerobic capacity declined below posttraining levels in HIIT and ENT (P < 0.05). Conclusions Six weeks of HIIT induced widespread adaptations before detraining in middle-age men. Exercise training-induced increases in aerobic capacity declined during 2.5 wk of detraining, but gains in lean mass and muscle strength were maintained.

Exercise training in combination with optimal nutritional support is an effective strategy to maintain or increase skeletal muscle mass. A single bout of resistance exercise undertaken with adequate protein availability increases rates of muscle protein synthesis and, when repeated over weeks and months, leads to increased muscle fiber size. While resistance-based training is considered the ‘gold standard’ for promoting muscle hypertrophy, other modes of exercise may be able to promote gains in muscle mass. High-intensity interval training (HIIT) comprises short bouts of exercise at or above the power output/speed that elicits individual maximal aerobic capacity, placing high tensile stress on skeletal muscle, and somewhat resembling the demands of resistance exercise. While HIIT induces rapid increases in skeletal muscle oxidative capacity, the anabolic potential of HIIT for promoting concurrent gains in muscle mass and cardiorespiratory fitness has received less scientific inquiry. In this review, we discuss studies that have determined muscle growth responses after HIIT, with a focus on molecular responses, that provide a rationale for HIIT to be implemented among populations who are susceptible to muscle loss (e.g. middle-aged or older adults) and/or in clinical settings (e.g. pre- or post-surgery).

Exercise training is recommended to improve cardiometabolic health and fertility in women with polycystic ovary syndrome (PCOS), yet there are few randomized controlled trials on the effects of different exercise protocols on clinical reproductive outcomes. Our aim was to determine the effect of high-intensity interval training (HIT) on menstrual frequency, as a proxy of reproductive function, in women with PCOS.The IMPROV-IT study was a two-center randomized controlled trial undertaken in Norway and Australia. Women with PCOS were eligible for inclusion. After stratification for body mass index27 or ≥27 kg·m-2 and study center, participants were randomly allocated (1:1:1) to high-volume HIT (HV-HIT), low-volume HIT (LV-HIT), or a control group. Measurements were assessed at baseline, after the 16-wk exercise intervention, and at 12-month follow-up. The primary outcome was menstrual frequency after 12 months. Secondary outcomes included markers of cardiometabolic and reproductive health, quality of life, and adherence to and enjoyment of HIT.We randomly allocated 64 participants to the HV-HIT (n = 20), LV-HIT (n = 21), or control group (n = 23). There were no differences in menstrual frequency at 12 months between the LV-HIT and control groups (frequency ratio, 1.02; 95% confidence interval [CI], 0.73-1.42), the HV-HIT and control groups (frequency ratio, 0.93; 95% CI, 0.67-1.29), or the LV-HIT and HV-HIT groups (frequency ratio, 1.09; 95% CI, 0.77-1.56). Menstrual frequency increased in all groups from baseline to 12 months. More participants became pregnant in the LV-HIT group (n = 5) than in the control group (n = 0, P = 0.02).A semisupervised HIT intervention did not increase menstrual frequency in women with PCOS.Clinical Trial Registration Number:ClinicalTrials.gov (NCT02419482).

Exercise training in combination with optimal nutritional support is an effective strategy to maintain or increase skeletal muscle mass. A single bout of resistance exercise undertaken with adequate protein availability increases rates of muscle protein synthesis and, when repeated over weeks and months, leads to increased muscle fiber size. While resistance-based training is considered the 'gold standard' for promoting muscle hypertrophy, other modes of exercise may be able to promote gains in muscle mass. High-intensity interval training (HIIT) comprises short bouts of exercise at or above the power output/speed that elicits individual maximal aerobic capacity, placing high tensile stress on skeletal muscle, and somewhat resembling the demands of resistance exercise. While HIIT induces rapid increases in skeletal muscle oxidative capacity, the anabolic potential of HIIT for promoting concurrent gains in muscle mass and cardiorespiratory fitness has received less scientific inquiry. In this review, we discuss studies that have determined muscle growth responses after HIIT, with a focus on molecular responses, that provide a rationale for HIIT to be implemented among populations who are susceptible to muscle loss (e.g. middle-aged or older adults) and/or in clinical settings (e.g. pre- or post-surgery).

Background & aims: Guidelines for reducing postprandial blood glucose concentrations include avoiding high glycemic index (GI) foods, such as white potatoes. However, GI testing is often undertaken in the morning with foods consumed in isolation by non-clinical cohorts. We investigated the impact of potato preparation and consumption as part of a mixed-evening meal on postprandial and nocturnal glycemic responses, and postprandial insulin response, in individuals with Type 2 Diabetes Mellitus (T2DM). Methods: In a randomized, cross-over design, 24 males and females (age 58.3 ± 9.3 y; BMI: 31.7 ± 6.8 kg/m ) with T2DM (diet or metformin controlled) completed four experimental trials after consuming a standardized breakfast (25% daily energy intake (EI)) and lunch (35% EI). Dinner (40% EI) was consumed at 1800 h being either: 1) boiled potato (BOIL); 2) roasted potato (ROAST); 3) boiled potato cooled for 24 h (COOLED); or 4) basmati rice (CONTROL). Each meal contained 50% carbohydrate, 30% fat and 20% protein. Blood samples were collected prior to, immediately post meal and at 30-min intervals for a further 120 min. A continuous glucose monitor was worn to assess nocturnal interstitial glucose concentrations. Results: No differences were detected in postprandial venous glucose area under the curve (iAUC) between CONTROL and all three potato conditions. Postprandial insulin iAUC was greater following COOLED compared to CONTROL (P = 0.003; 95% CI: 18.9–111.72 miU/mL). No significant differences between CONTROL and BOIL or ROAST were detected for postprandial insulin concentrations. All potato meals resulted in lower nocturnal glucose AUC than CONTROL (P < 0.001; 95% CI 4.15–15.67 mmol/L x h). Conclusion: Compared to an isoenergetic rice meal, boiled, roasted or boiled then cooled potato-based meals were not associated with unfavourable postprandial glucose responses or nocturnal glycemic control, and can be considered suitable for individuals with T2DM when consumed as part of a mixed-evening meal. Clinical trial registration: Australian New Zealand Clinical Trials Registry https://www.anzctr.org.au/, ACTRN 12618000480280. 2

When ingested alone, beetroot juice and sodium bicarbonate are ergogenic for high-intensity exercise performance. This study sought to determine the independent and combined effects of these supplements. Eight endurance trained (VO2max 65 mL·kg·min-1) male cyclists completed four × 4-km time trials (TT) in a doubleblind Latin square design supplementing with beetroot crystals (BC) for 3 days (15 g·day-1 + 15 g 1 h before TT, containing 300 mg nitrate per 15 g), bicarbonate (Bi 0.3 g·kg-1 body mass [BM] in 5 doses every 15 min from 2.5 h before TT); BC+Bi or placebo (PLA). Subjects completed TTs on a Velotron cycle ergometer under standardized laboratory conditions. Plasma nitrite concentrations were significantly elevated only in the BC+Bi trial before the TT (1520 ± 786 nmol·L-1) compared with baseline (665 ± 535 nmol·L-1, p = .02) and the Bi and PLA conditions (Bi: 593 ± 203 nmol·L-1, p < .01; PLA: 543 ± 369 nmol·L-1, p < .01). Plasma nitrite concentrations were not elevated in the BC trial before the TT (1102 ± 218 nmol·L-1) compared with baseline (975 ± 607 nmol·L-1, p > .05). Blood bicarbonate concentrations were increased in the BC+Bi and Bi trials before the TT (BC+Bi: 30.9 ± 2.8 mmol·L-1; Bi: 31.7 ± 1.1 mmol·L-1). There were no differences in mean power output (386–394 W) or the time taken to complete the TT (335.8–338.1 s) between any conditions. Under the conditions of this study, supplementation was not ergogenic for 4-km TT performance.

Background: A physically active lifestyle is recommended to improve cardiometabolic health and fertility in women with polycystic ovary syndrome (PCOS), yet there are few randomized controlled trials investigating the effects of different exercise protocols on clinical reproductive outcomes. Our aim was to determine the effect of high-intensity interval training (HIT) on menstrual frequency, as a proxy of reproductive function, in women with PCOS. Methods: The IMPROV-IT study was a two-centre randomized controlled trial undertaken in Norway and Australia. Women with PCOS (Rotterdam criteria) were eligible for inclusion. After stratification for body mass index < or ≥27 kg/m2 and study centre, participants were randomly allocated by computer-generated random numbers (1:1:1) to high-volume HIT (HV-HIT), low-volume HIT (LV-HIT), or a control group. Measurements were assessed at baseline, after the 16-week exercise intervention and at 12-months follow-up. The primary outcome was menstrual frequency after 12 months. Secondary outcomes included markers of cardiometabolic and reproductive health, quality of life, and adherence to and enjoyment of HIT. Analysis was by intention-to-treat. Findings: The study took place between June 2015 and February 2020. We randomly allocated 64 participants to HV-HIT (n=20), LV-HIT (n=21), or the control group (n=23). There were no difference in menstrual frequency at 12 months between LV-HIT and control (frequency-ratio 0·09, 95%CI 0·06-0·12), HV-HIT and control (frequency-ratio 0·07, 95%CI 0·05-0·10) or LV-HIT and HV-HIT (frequency-ratio 0·09, 95%CI 0·07-0·13). More participants became pregnant in the LV-HIT group (n=5, 33·3%) than in the control group (n=0, p=0·02). Interpretation: HIT did not improve menstrual frequency in women with PCOS, but significantly increased pregnancy rate. Trial Registration: The study was registered in ClinicalTrials.gov (NCT02419482). Funding Statement: The Liaison Committee for Education, Research and Innovation in Central Norway, Norwegian University of Science and Technology, Australian Catholic University. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: Ethics approval was obtained from the Regional Committee for Medical and Health Research Ethics in Central Norway (REK-midt 2015/468) and the ACU Human Research Ethics Committee (2017-260H). The procedures for data entry, coding, and storage have been approved by the Regional Committee Medical Research Ethics in Central Norway. All participants were informed about the experimental protocol and potential risks verbally and in writing before providing their written informed consent.

Objective This study determined the effects of 16-week high-dairy-protein, variable-carbohydrate (CHO) diets and exercise training (EXT) on body composition in men and women with overweight/obesity. Methods One hundred and eleven participants (age 47 ± 6 years, body mass 90.9 ± 11.7 kg, BMI 33 ± 4 kg/m2, values mean ± SD) were randomly stratified to diets with either: high dairy protein, moderate CHO (40% CHO: 30% protein: 30% fat; ∼4 dairy servings); high dairy protein, high CHO (55%: 30%: 15%; ∼4 dairy servings); or control (55%: 15%: 30%; ∼1 dairy serving). Energy restriction (500 kcal/day) was achieved through diet (∼250 kcal/day) and EXT (∼250 kcal/day). Body composition was measured using dual-energy X-ray absorptiometry before, midway, and upon completion of the intervention. Results Eighty-nine (25 M/64 F) of 115 participants completed the 16-week intervention, losing 7.7 ± 3.2 kg fat mass (P

Purpose: We determined the effect of suppressing lipolysis via administration of Nicotinic acid (NA) and pre-exercise feeding on rates of whole-body substrate utilisation and cycling time trial (TT) performance. Methods: In a randomised, single-blind, crossover design, eight trained male cyclists/triathletes completed two series of TTs in which they performed a predetermined amount of work calculated to last ~60, 90 and 120 min. TTs were undertaken after a standardised breakfast (2 g kg−1 BM of carbohydrate (CHO)) and ingestion of capsules containing either NA or placebo (PL). Results: Plasma [free fatty acids] were suppressed with NA, but increased in the later stages of TT90 and TT120 with PL (p < 0.05). There was no treatment effect on time to complete TT60 (60.4 ± 4.1 vs. 59.3 ± 3.4 min) or TT90 (90.4 ± 9.1 vs. 89.5 ± 6.6 min) for NA and PL, respectively. However, TT120 was slower with NA (123.1 ± 5.7 vs. 120.1 ± 8.7 min, p < 0.001), which coincided with a decline in plasma [glucose] during the later stages of this ride (p < 0.05). For TTs of the same duration, the rates of whole-body CHO oxidation were unaffected by NA, but decreased with increasing TT time (p < 0.05). CHO was the predominant substrate for all TTs contributing between 83 and 94 % to total energy expenditure, although there was a small use of lipid-based fuels for all rides. Conclusion: (1) NA impaired cycling TT performance lasting 120 min, (2) cycling TTs lasting from 60 to 120 min are CHO dependent, and (3) there is an obligatory use of lipid-based fuels in TTs lasting 1–2 h.

Individuals with type 2 diabetes (T2D) require a long-term dietary strategy for blood glucose management and may benefit from time-restricted eating (TRE, where the duration between the first and last energy intake is restricted to 8&ndash, 10 h/day). We aimed to determine the feasibility of TRE for individuals with T2D. Participants with T2D (HbA1c &gt, 6.5 to &lt, 9%, eating window &gt, 12 h/day) were recruited to a pre-post, non-randomised intervention consisting of a 2-week Habitual period to establish baseline dietary intake, followed by a 4-weeks TRE intervention during which they were instructed to limit all eating occasions to between 10:00 and 19:00 h on as many days of each week as possible. Recruitment, retention, acceptability, and safety were recorded throughout the study as indicators of feasibility. Dietary intake, glycaemic control, psychological well-being, acceptability, cognitive outcomes, and physiological measures were explored as secondary outcomes. From 594 interested persons, and 27 eligible individuals, 24 participants enrolled and 19 participants (mean &plusmn, SD, age: 50 &plusmn, 9 years, BMI: 34 &plusmn, 5 kg/m2, HbA1c: 7.6 &plusmn, 1.1%) completed the 6-week study. Overall daily dietary intake did not change between Habitual (~8400 kJ/d, 35% carbohydrate, 20% protein, 41% fat, 1% alcohol) and TRE periods (~8500 kJ/d, 35% carbohydrate, 19% protein, 42% fat, 1% alcohol). Compliance to the 9 h TRE period was 72 &plusmn, 24% of 28 days (i.e., ~5 days/week), with varied adherence (range: 4&ndash, 100%). Comparisons of adherent vs. non-adherent TRE days showed that adherence to the 9-h TRE window reduced daily energy intake through lower absolute carbohydrate and alcohol intakes. Overall, TRE did not significantly improve measures of glycaemic control (HbA1c &minus, 0.2 &plusmn, 0.4%, p = 0.053) or reduce body mass. TRE did not impair or improve psychological well-being, with variable effects on cognitive function. Participants described hunger, daily stressors, and emotions as the main barriers to adherence. We demonstrate that 4-weeks of TRE is feasible and achievable for these individuals with T2D to adhere to for at least 5 days/week. The degree of adherence to TRE strongly influenced daily energy intake. Future trials may benefit from supporting participants to incorporate TRE in regular daily life and to overcome barriers to adherence.

Two independent but inter-related conditions that have a growing impact on healthy life expectancy and health care costs in developed nations are an age-related loss of muscle mass (i.e., sarcopenia) and obesity. Sarcopenia is commonly exacerbated in overweight and obese individuals. Progression towards obesity promotes an increase in fat mass and a concomitant decrease in muscle mass, producing an unfavourable ratio of fat to muscle. The coexistence of diminished muscle mass and increased fat mass (so-called 'sarcobesity') is ultimately manifested by impaired mobility and/or development of life-style-related diseases. Accordingly, the critical health issue for a large proportion of adults in developed nations is how to lose fat mass while preserving muscle mass. Lifestyle interventions to prevent or treat sarcobesity include energy-restricted diets and exercise. The optimal energy deficit to reduce body mass is controversial. While energy restriction in isolation is an effective short-term strategy for rapid and substantial weight loss, it results in a reduction of both fat and muscle mass and therefore ultimately predisposes one to an unfavourable body composition. Aerobic exercise promotes beneficial changes in whole-body metabolism and reduces fat mass, while resistance exercise preserves lean (muscle) mass. Current evidence strongly supports the inclusion of resistance and aerobic exercise to complement mild energy-restricted high-protein diets for healthy weight loss as a primary intervention for sarcobesity.

Alcohol ingestion decreases postexercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation is unknown. Autophagy is an intracellular “recycling” system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise. In a randomized crossover design, eight physically active males completed three experimental trials of concurrent exercise with either postexercise ingestion of alcohol and carbohydrate (12 ± 2 standard drinks; ALC-CHO), energy-matched alcohol and protein (ALC-PRO), or protein (PRO) only. Muscle biopsies were taken at rest and 2 and 8 h postexercise. Select autophagy-related gene (Atg) proteins decreased compared with rest with ALC-CHO ( P < 0.05) but not ALC-PRO. There were parallel increases ( P < 0.05) in p62 and PINK1 commensurate with a reduction in BNIP3 content, indicating a diminished capacity for mitochondria-specific autophagy (mitophagy) when alcohol and carbohydrate were coingested. DNA fragmentation increased in both alcohol conditions ( P < 0.05); however, nuclear AIF accumulation preceded this apoptotic response with ALC-CHO only ( P < 0.05). In contrast, increases in the nuclear content of p53, TFEB, and PGC-1α in ALC-PRO were accompanied by markers of mitochondrial biogenesis at the transcriptional ( Tfam, SCO2, and NRF-1) and translational (COX-IV, ATPAF1, and VDAC1) level ( P < 0.05). We conclude that alcohol ingestion following exercise triggers apoptosis, whereas the anabolic properties of protein coingestion may stimulate mitochondrial biogenesis to protect cellular homeostasis.

We compared the impact of a high versus low energy intake first meal on glucose and insulin responses during prolonged sitting in individuals with prediabetes. Thirteen adults with overweight/obesity and prediabetes (mean &plusmn, SD age: 60 &plusmn, 6 years, BMI: 33 &plusmn, 4 kg/m2, 2 h OGTT: 8.9 &plusmn, 1.1 mmol/L) completed two randomised trials: 10 h uninterrupted sitting, incorporating three meals with matching macronutrient compositions but different energy distributions: High-Energy Breakfast (HE-BF, breakfast: 50%, lunch: 30%, dinner: 20% energy intake), Low-Energy Breakfast (LE-BF: 20%/30%/50% energy intake). Venous blood was sampled from 08:00&ndash, 18:00 h for determination of plasma glucose and insulin concentrations, with 24 h continuous glucose monitoring (CGM). Total glucose area under the curve (AUC, +5.7 mmol/L/h, p = 0.019) and mean plasma glucose concentrations (+0.5 mmol/L, p = 0.014) were greater after HE-BF compared to LE-BF. In the HE-BF condition, compared to LE-BF, there was a greater incremental area under the curve (iAUC) for plasma glucose post-breakfast (+44 &plusmn, 59%, p = 0.007), but lower iAUC post-lunch (&minus, 55 &plusmn, 36%, p &lt, 0.001). Total insulin AUC was greater (+480 mIU/mL/h, p &lt, 0.01) after HE-BF compared to LE-BF. Twenty-four-hour (24 h) CGM revealed no differences in mean glucose and total AUC between conditions. Compared to a low-energy first meal, a high-energy first meal elicited exaggerated plasma insulin and glucose responses until lunch but had little effect on 24 h glycaemia. During periods of prolonged sitting, adults with prediabetes may have more beneficial postprandial insulin responses to a low-energy first meal.

Background: Interactions between diet, physical activity and genetic predisposition contribute to variable body mass changes observed in response to weight loss interventions. Circulating microRNAs (c-miRNAs) may act as ‘biomarkers’ that are associated with the rate of change in weight loss, and/or play a role in regulating the biological variation, in response to energy restriction. Objective: To quantify targeted c-miRNAs with putative roles in energy metabolism and exercise adaptations following a 16 wk diet and exercise intervention in individuals with large (high responders; HiRes) versus small (low responders; LoRes) losses in body mass. Methods: From 89 male and female overweight/obese participants who completed the intervention (energy restriction from diet, 250 kcal/d, and exercise, 250 kcal/d), subgroups of HiRes ( > 10% body mass loss, n = 22) and LoRes ( < 5% body mass loss, n = 18) were identified. From resting plasma samples collected after an overnight fast pre and post intervention, RNA was extracted, quantified and reverse transcribed. Thirteen c-miRNA selected a priori were analysed using a customised 96-well miScript miRNA PCR Array. Results: Loss of body mass (-11.0 ± 2.3 kg vs. -3.0 ± 1.3 kg; P < 0.01) and fat mass (-11.1 ± 2.6 kg vs. -3.9 ± 1.6 kg; P < 0.01) was greater for HiRes than LoRes (P < 0.001). Expression of c-miR-935 was higher in LoRes compared to HiRes pre- (~47%; P = 0.025) and post- (~100%; P < 0.01) intervention and was the only c-miRNA differentially expressed at baseline between groups. The abundance of c-miR-221-3p and -223-3p increased pre- to post-intervention in both groups (~57–69% and ~25–90%, P < 0.05). There was a post-intervention increase in c-miR-140 only in LoRes compared to HiRes (~23%, P = 0.016). Conclusion: The differential expression and responses of selected c-miRNAs in overweight/obese individuals to an exercise and diet intervention suggests a putative role for these ‘biomarkers’ in the prediction or detection of individual variability to weight loss interventions.