People with obesity exhibit losses in muscle proteostasis that are partly improved by exercise training.

This pilot experiment examines if a loss in muscle proteostasis occurs in people with obesity and whether endurance exercise positively influences either the abundance profile or turnover rate of proteins in this population. Men with (n = 3) or without (n = 4) obesity were recruited and underwent a 14-d measurement protocol of daily deuterium oxide (D2 O) consumption and serial biopsies of vastus lateralis muscle. Men with obesity then completed 10-weeks of high-intensity interval training (HIIT), encompassing 3 sessions per week of cycle ergometer exercise with 1 min intervals at 100% maximum aerobic power interspersed by 1 min recovery periods. The number of intervals per session progressed from 4 to 8, and during weeks 8-10 the 14-d measurement protocol was repeated. Proteomic analysis detected 352 differences (p < 0.05, false discovery rate < 5%) in protein abundance and 19 (p < 0.05) differences in protein turnover, including components of the ubiquitin-proteasome system. HIIT altered the abundance of 53 proteins and increased the turnover rate of 22 proteins (p < 0.05) and tended to benefit proteostasis by increasing muscle protein turnover rates. Obesity and insulin resistance are associated with compromised muscle proteostasis, which may be partially restored by endurance exercise.

Post-exercise recovery for the endurance athlete with type 1 diabetes: a consensus statement.

There has been substantial progress in the knowledge of exercise and type 1 diabetes, with the development of guidelines for optimal glucose management. In addition, an increasing number of people living with type 1 diabetes are pushing their physical limits to compete at the highest level of sport. However, the post-exercise recovery routine, particularly with a focus on sporting performance, has received little attention within the scientific literature, with most of the focus being placed on insulin or nutritional adaptations to manage glycaemia before and during the exercise bout. The post-exercise recovery period presents an opportunity for maximising training adaption and recovery, and the clinical management of glycaemia through the rest of the day and overnight. The absence of clear guidance for the post-exercise period means that people with type 1 diabetes should either develop their own recovery strategies on the basis of individual trial and error, or adhere to guidelines that have been developed for people without diabetes. This Review provides an up-to-date consensus on post-exercise recovery and glucose management for individuals living with type 1 diabetes. We aim to: (1) outline the principles and time course of post-exercise recovery, highlighting the implications and challenges for endurance athletes living with type 1 diabetes; (2) provide an overview of potential strategies for post-exercise recovery that could be used by athletes with type 1 diabetes to optimise recovery and adaptation, alongside improved glycaemic monitoring and management; and (3) highlight the potential for technology to ease the burden of managing glycaemia in the post-exercise recovery period.

The Comparative Methylome and Transcriptome After Change of Direction Compared to Straight Line Running Exercise in Human Skeletal Muscle.

The methylome and transcriptome signatures following exercise that are physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g., high intensity interval training/HIIT) has not been investigated. To explore this, we performed two different sport/exercise relevant high-intensity running protocols in five male sport team members using a repeated measures design of: (1) change of direction (COD) versus; (2) straight line (ST) running exercise with a wash-out period of at least 2 weeks between trials. Skeletal muscle biopsies collected from the vastus lateralis 30 min and 24 h post exercise, were assayed using 850K methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes was performed. Despite COD and ST exercise being matched for classically defined intensity measures (speed × distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) exertion measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity. The exercise response alone across both conditions evoked extensive alterations in the methylome 30 min and 24 h post exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST exercise, particularly at 30 min post exercise, enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of genes that were altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we observed that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We also confirmed increased gene expression of VEGFA, and considerably larger increases in the expression of canonical metabolic genes PPARGC1A (that encodes PGC1-α) and NR4A3 in COD vs. ST exercise. Overall, we demonstrate that increased physiological/metabolic load via COD exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise.

Young, healthy males and females present cardiometabolic protection against the detrimental effects of a 7-day high-fat high-calorie diet.

PURPOSE: High-fat, high-calorie (HFHC) diets have been used as a model to investigate lipid-induced insulin resistance. Short-term HFHC diets reduce insulin sensitivity in young healthy males, but to date, no study has directly compared males and females to elucidate sex-specific differences in the effects of a HFHC diet on functional metabolic and cardiovascular outcomes. METHODS: Eleven males (24 ± 4 years; BMI 23 ± 2 kg.m-2; V̇O2 peak 62.3 ± 8.7 ml.min-1.kg-1FFM) were matched to 10 females (25 ± 4 years; BMI 23 ± 2 kg.m-2; V̇O2 peak 58.2 ± 8.2 ml.min-1.kg-1FFM). Insulin sensitivity, measured via oral glucose tolerance test, metabolic flexibility, arterial stiffness, body composition and blood lipids and liver enzymes were measured before and after 7 days of a high-fat (65% energy) high-calorie (+ 50% kcal) diet. RESULTS: The HFHC diet did not change measures of insulin sensitivity, metabolic flexibility or arterial stiffness in either sex. There was a trend towards increased total body fat mass (kg) after the HFHC diet (+ 1.8% and + 2.3% for males and females, respectively; P = 0.056). In contrast to females, males had a significant increase in trunk to leg fat mass ratio (+ 5.1%; P = 0.005). CONCLUSION: Lean, healthy young males and females appear to be protected from the negative cardio-metabolic effects of a 7-day HFHC diet. Future research should use a prolonged positive energy balance achieved via increased energy intake and reduced energy expenditure to exacerbate negative metabolic and cardiovascular functional outcomes to determine whether sex-specific differences exist under more metabolically challenging conditions.

Glycogen Utilization during Running: Intensity, Sex, and Muscle-Specific Responses.

PURPOSE: This study aimed to quantify net glycogen utilization in the vastus lateralis (VL) and gastrocnemius (G) of male (n = 11) and female (n = 10) recreationally active runners during three outdoor training sessions. METHODS: After 2-d standardization of carbohydrate intakes (6 g·kg body mass per day), glycogen was assessed before and after 1) a 10-mile road run (10-mile) at lactate threshold, 2) 8 × 800-m track intervals (8 × 800 m) at velocity at V˙O2max, and 3) 3 × 10-min track intervals (3 × 10 min) at lactate turnpoint. RESULTS: Resting glycogen concentration was lower in the G of female compared with males (P < 0.001) runners, although no sex differences were apparent in the VL (P = 0.40). Within the G and VL of male runners, net glycogen utilization differed between training sessions where 10 miles was greater than both track sessions (all comparisons, P < 0.05). In contrast, net glycogen utilization in female runners was not different between training sessions in either muscle (all comparisons, P > 0.05). Net glycogen utilization was greater in male than in female runners in both VL (P = 0.02) and G (P = 0.07) during the 10-mile road run. With the exception of male runners during the 3 × 10-min protocol (P = 0.28), greater absolute glycogen utilization was observed in the G versus the VL muscle in both male and female runners and during all training protocols (all comparisons, P < 0.05). CONCLUSION: Data demonstrate that 1) prolonged steady-state running necessitates a greater glycogen requirement than shorter but higher-intensity track running sessions, 2) female participants display evidence of reduced resting muscle glycogen concentration and net muscle glycogen utilization when compared with male participants, and 3) net glycogen utilization is higher in the G muscle compared with the VL.

Reliability of Protein Abundance and Synthesis Measurements in Human Skeletal Muscle.

The repeatability of dynamic proteome profiling (DPP), which is a novel technique for measuring the relative abundance (ABD) and fractional synthesis rate (FSR) of proteins in humans, is investigated. LC-MS analysis is performed on muscle samples taken from male participants (n = 4) that consumed 4 × 50 mL doses of deuterium oxide (2 H2 O) per day for 14 days. ABD is measured by label-free quantitation and FSR is calculated from time-dependent changes in peptide mass isotopomer abundances. One-hundred one proteins have at least one unique peptide and are used in the assessment of protein ABD. Fifty-four of these proteins meet more stringent criteria and are used in the assessment of FSR data. The median (M), lower-, (Q1 ) and upper-quartile (Q3 ) values for protein FSR (%/d) are M = 1.63, Q1  = 1.07, and Q3  = 3.24, respectively. The technical CV of ABD data has a median value of 3.6% (Q1 1.7% to Q3 6.7%), whereas the median CV of FSR data is 10.1% (Q1 3.5% to Q3 16.5%). These values compare favorably against other assessments of technical repeatability of proteomics data, which often set a CV of 20% as the upper bound of acceptability.

Home-based high-intensity interval training reduces barriers to exercise in people with type 1 diabetes.

NEW FINDINGS: What is the topic of this review? This symposium review provides an overview of the recent work investigating whether a virtually monitored home-based high-intensity interval training (Home-HIT) intervention reduces the fear of hypoglycaemia and other common barriers to exercise in people with type 1 diabetes. What advances does it highlight? Home-HIT seems to offer a strategy to reduce fear of hypoglycaemia, while simultaneously removing other known barriers that prevent people with type 1 diabetes from taking up exercise, because it is time efficient, requires no travel time or costs associated with gym memberships, and allows people to exercise in their chosen environment. ABSTRACT: People with type 1 diabetes (T1D) are recommended to engage in regular exercise for a variety of health and fitness reasons. However, many lead a sedentary lifestyle and fail to meet the physical activity guidelines, in part because of the challenge of managing blood glucose concentration and fear of hypoglycaemia. A number of strategies designed to help people with T1D to manage their blood glucose during and after exercise have been investigated. Although many of these strategies show promise in facilitating blood glucose management during and after exercise, they do not target the many other common barriers to exercise that people with T1D face, such as difficulty with cost and travel time to gyms, limited access to exercise bikes and treadmills, and a possible dislike of exercising in front of others in public places. In this symposium review, we provide an overview of ongoing research into a virtually monitored home-based high-intensity interval training (Home-HIT) programme that is designed to reduce these other common barriers to exercise. The conclusion of this review is that Home-HIT seems to offer a strategy to reduce fear of hypoglycaemia, while simultaneously removing other known barriers preventing people with T1D from taking up exercise, such as being time efficient, requiring no travel time or costs associated with gym memberships, and giving them the opportunity to exercise in their chosen environment, reducing the embarrassment experienced by some when exercising in public.

A Multidisciplinary Evaluation of a Virtually Supervised Home-Based High-Intensity Interval Training Intervention in People With Type 1 Diabetes.

OBJECTIVE: Adopt a multidisciplinary approach to evaluate a virtually supervised home-based high-intensity interval training (Home-HIT) intervention in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: Eleven individuals with type 1 diabetes (seven women; age 30 ± 3 years; [Formula: see text] 2.5 ± 0.2 L/min; duration of diabetes 10 ± 2 years) completed 6 weeks of Home-HIT. A heart rate monitor and mobile phone application were used to provide feedback to the participants and research team on exercise intensity (compliance) and adherence. RESULTS: Training adherence was 95 ± 2%, and compliance was 99 ± 1%. Home-HIT increased [Formula: see text] by 7% (P = 0.017) and decreased insulin dose by 13% (P = 0.012). Blood glucose concentration did not change from baseline to immediately or 1 h post Home-HIT. Qualitative perceptions of Home-HIT and the virtual-monitoring system were positive, supporting that the intervention successfully removed exercise barriers in people with type 1 diabetes. CONCLUSIONS: Virtually monitored Home-HIT resulted in high adherence alongside increased [Formula: see text] and decreased insulin dose.

Post-exercise carbohydrate and energy availability induce independent effects on skeletal muscle cell signalling and bone turnover: implications for training adaptation.

KEY POINTS: Reduced carbohydrate (CHO) availability before and after exercise may augment endurance training-induced adaptations of human skeletal muscle, as mediated via modulation of cell signalling pathways. However, it is not known whether such responses are mediated by CHO restriction, energy restriction or a combination of both. In recovery from a twice per day training protocol where muscle glycogen concentration is maintained within 200-350 mmol kg-1 dry weight (dw), we demonstrate that acute post-exercise CHO and energy restriction (i.e. < 24 h) does not potentiate potent cell signalling pathways that regulate hallmark adaptations associated with endurance training. In contrast, consuming CHO before, during and after an acute training session attenuated markers of bone resorption, effects that are independent of energy availability. Whilst the enhanced muscle adaptations associated with CHO restriction may be regulated by absolute muscle glycogen concentration, the acute within-day fluctuations in CHO availability inherent to twice per day training may have chronic implications for bone turnover. ABSTRACT: We examined the effects of post-exercise carbohydrate (CHO) and energy availability (EA) on potent skeletal muscle cell signalling pathways (regulating mitochondrial biogenesis and lipid metabolism) and indicators of bone metabolism. In a repeated measures design, nine males completed a morning (AM) and afternoon (PM) high-intensity interval (HIT) (8 × 5 min at 85% V̇O2peak ) running protocol (interspersed by 3.5 h) under dietary conditions of (1) high CHO availability (HCHO: CHO ∼12 g kg-1 , EA∼ 60 kcal kg-1 fat free mass (FFM)), (2) reduced CHO but high fat availability (LCHF: CHO ∼3 (-1 , EA∼ 60 kcal kg-1 FFM) or (3), reduced CHO and reduced energy availability (LCAL: CHO ∼3 g kg-1 , EA∼ 20 kcal kg-1 FFM). Muscle glycogen was reduced to ∼200 mmol kg-1  dw in all trials immediately post PM HIT (P < 0.01) and remained lower at 17 h (171, 194 and 316 mmol kg-1  dw) post PM HIT in LCHF and LCAL (P < 0.001) compared to HCHO. Exercise induced comparable p38MAPK phosphorylation (P < 0.05) immediately post PM HIT and similar mRNA expression (all P < 0.05) of PGC-1α, p53 and CPT1 mRNA in HCHO, LCHF and LCAL. Post-exercise circulating ßCTX was lower in HCHO (P < 0.05) compared to LCHF and LCAL whereas exercise-induced increases in IL-6 were larger in LCAL (P < 0.05) compared to LCHF and HCHO. In conditions where glycogen concentration is maintained within 200-350 mmol kg-1  dw, we conclude post-exercise CHO and energy restriction (i.e. < 24 h) does not potentiate cell signalling pathways that regulate hallmark adaptations associated with endurance training. In contrast, consuming CHO before, during and after HIT running attenuates bone resorption, effects that are independent of energy availability and circulating IL-6.

High-Intensity Interval Training Improves Aerobic Capacity Without a Detrimental Decline in Blood Glucose in People With Type 1 Diabetes.

Context: We investigated whether 6 weeks of high-intensity interval training (HIT) induced improvements in cardiometabolic health markers similar to moderate-intensity continuous training (MICT) in people with type 1 diabetes (T1D), and whether HIT abolished acute reductions in plasma glucose levels observed after MICT sessions. Methods: Two groups of sedentary individuals with T1D (n = 7 per group) completed 6 weeks of thrice weekly HIT or MICT. Pre- and post-training measurements were made of 24-hour interstitial glucose profiles, using continuous glucose monitors, and cardiometabolic health markers [peak oxygen consumption (V˙o2peak), blood lipid profile, and aortic pulse wave velocity (aPWV)]. Capillary blood glucose (BG) concentrations were assessed before and after exercise to investigate changes in BG levels during exercise in the fed state. Results: Six weeks of HIT or MICT increased V˙o2peak by 14% and 15%, respectively (P < 0.001), and aPWV by 12% (P < 0.001), with no difference between groups. There was no difference in incidence or percentage of time spent in hypoglycemia after training in either group (P > 0.05). In the fed state, the mean change (±SEM) in capillary BG concentration during the HIT sessions was -0.2 ± 0.5 mmol/L, and -5.5 ± 0.4 mmol/L during MICT. Conclusions: Six weeks of HIT improved V˙o2peak and aPWV to a similar extent as MICT. That BG levels remained stable during HIT in the fed state but consistently fell during MICT suggests HIT may be the preferred training mode for some people with T1D.

Fasted High-Intensity Interval and Moderate-Intensity Exercise Do Not Lead to Detrimental 24-Hour Blood Glucose Profiles.

Aims: To compare the effect of a bout of high-intensity interval training (HIT) with a bout of moderate-intensity continuous training (MICT) on glucose concentrations over the subsequent 24-hour period. Methods: Fourteen people with type 1 diabetes [T1D (duration of T1D, 8.2 ± 1.4 years)], all on a basal-bolus regimen, completed a randomized, counterbalanced, crossover study. Continuous glucose monitoring was used to assess glycemic control after a single bout of HIT (six 1-minute intervals) and 30 minutes of MICT on separate days compared with a nonexercise control day (CON). Exercise was undertaken after an overnight fast with omission of short-acting insulin. Capillary blood glucose samples were recorded before and after exercise to assess the acute changes in glycemia during HIT and MICT. Results: There was no difference in the incidence of or percentage of time spent in hypoglycemia, hyperglycemia, or target glucose range over the 24-hour and nocturnal period (12:00 am to 6:00 am) between CON, HIT, and MICT (P > 0.05). Blood glucose concentrations were not significantly (P = 0.49) different from pre-exercise to post-exercise, with HIT (0.39 ± 0.42 mmol/L) or MICT (-0.39 ± 0.66 mmol/L). There was no difference between exercise modes (P = 1.00). Conclusions: HIT or 30 minutes of MICT can be carried out after an overnight fast with no increased risk of hypoglycemia or hyperglycemia. If the pre-exercise glucose concentration is 7 to 14 mmol/L, no additional carbohydrate ingestion is necessary to undertake these exercises. Because HIT is a time-efficient form of exercise, the efficacy and safety of long-term HIT should now be explored.