Implications of Heat Stress-induced Metabolic Alterations for Endurance Training.

Inducing a heat-acclimated phenotype via repeated heat stress improves exercise capacity and reduces athletes̓ risk of hyperthermia and heat illness. Given the increased number of international sporting events hosted in countries with warmer climates, heat acclimation strategies are increasingly popular among endurance athletes to optimize performance in hot environments. At the tissue level, completing endurance exercise under heat stress may augment endurance training adaptation, including mitochondrial and cardiovascular remodeling due to increased perturbations to cellular homeostasis as a consequence of metabolic and cardiovascular load, and this may improve endurance training adaptation and subsequent performance. This review provides an up-to-date overview of the metabolic impact of heat stress during endurance exercise, including proposed underlying mechanisms of altered substrate utilization. Against this metabolic backdrop, the current literature highlighting the role of heat stress in augmenting training adaptation and subsequent endurance performance will be presented with practical implications and opportunities for future research.

Acute heat stress amplifies exercise-induced metabolomic perturbations and reveals variation in circulating amino acids in endurance-trained males.

NEW FINDINGS: What is the central question of this study? Whole-body substrate utilisation is altered during exercise in hot environments, characterised by increased glycolytic metabolism: does heat stress alter the serum metabolome in response to high intensity exercise? What are the main finding and its importance? Alongside increases in glycolytic metabolite abundance, circulating amino acid concentrations are reduced following exercise under heat stress. Prior research has overlooked the impact of heat stress on protein metabolism during exercise, raising important practical implications for protein intake recommendations in the heat. ABSTRACT: Using untargeted metabolomics, we aimed to characterise the systemic impact of environmental heat stress during exercise. Twenty-three trained male triathletes ( V ̇ O 2 peak ${\dot V_{{{\rm{O}}_2}{\rm{peak}}}}$  = 64.8 ± 9.2 ml kg min-1 ) completed a 30-min exercise test in hot (35°C) and temperate (21°C) conditions. Venous blood samples were collected immediately pre- and post-exercise, and the serum fraction was assessed via untargeted 1 H-NMR metabolomics. Data were analysed via uni- and multivariate analyses to identify differences between conditions. Mean power output was higher in temperate (231 ± 36 W) versus hot (223 ± 31 W) conditions (P < 0.001). Mean heart rate (temperate, 162 ± 10 beats min-1 , hot, 167 ± 9 beats min-1 , P < 0.001), peak core temperature (Trec ), core temperature change (ΔTrec ) (P < 0.001) and peak rating of perceived exertion (P = 0.005) were higher in hot versus temperate conditions. Change in metabolite abundance following exercise revealed distinct clustering following multivariate analysis. Six metabolites increased (2-hydroxyvaleric acid, acetate, alanine, glucarate, glucose, lactate) in hot relative to temperate (P < 0.05) conditions. Leucine and lysine decreased in both conditions but to a greater extent in temperate conditions (P < 0.05). Citrate (P = 0.04) was greater in temperate conditions whilst creatinine decreased in hot conditions only (P > 0.05). Environmental heat stress increased glycolytic metabolite abundance and led to distinct alterations in the circulating amino acid availability, including increased alanine, glutamine, leucine and isoleucine. The data highlight the need for additional exercise nutrition and metabolism research, specifically focusing on protein requirements for exercise under heat stress.

Carbohydrate improves exercise capacity but does not affect subcellular lipid droplet morphology, AMPK and p53 signalling in human skeletal muscle.

KEY POINTS: Muscle glycogen and intramuscular triglycerides (IMTG, stored in lipid droplets) are important energy substrates during prolonged exercise. Exercise-induced changes in lipid droplet (LD) morphology (i.e. LD size and number) have not yet been studied under nutritional conditions typically adopted by elite endurance athletes, that is, after carbohydrate (CHO) loading and CHO feeding during exercise. We report for the first time that exercise reduces IMTG content in both central and peripheral regions of type I and IIa fibres, reflective of decreased LD number in both fibre types whereas reductions in LD size were exclusive to type I fibres. Additionally, CHO feeding does not alter subcellular IMTG utilisation, LD morphology or muscle glycogen utilisation in type I or IIa/II fibres. In the absence of alterations to muscle fuel selection, CHO feeding does not attenuate cell signalling pathways with regulatory roles in mitochondrial biogenesis. ABSTRACT: We examined the effects of carbohydrate (CHO) feeding on lipid droplet (LD) morphology, muscle glycogen utilisation and exercise-induced skeletal muscle cell signalling. After a 36 h CHO loading protocol and pre-exercise meal (12 and 2 g kg-1 , respectively), eight trained males ingested 0, 45 or 90 g CHO h-1 during 180 min cycling at lactate threshold followed by an exercise capacity test (150% lactate threshold). Muscle biopsies were obtained pre- and post-completion of submaximal exercise. Exercise decreased (P < 0.01) glycogen concentration to comparable levels (∼700 to 250 mmol kg-1 DW), though utilisation was greater in type I (∼40%) versus type II fibres (∼10%) (P < 0.01). LD content decreased in type I (∼50%) and type IIa fibres (∼30%) (P < 0.01), with greater utilisation in type I fibres (P < 0.01). CHO feeding did not affect glycogen or IMTG utilisation in type I or II fibres (all P > 0.05). Exercise decreased LD number within central and peripheral regions of both type I and IIa fibres, though reduced LD size was exclusive to type I fibres. Exercise induced (all P < 0.05) comparable AMPKThr172 (∼4-fold), p53Ser15 (∼2-fold) and CaMKIIThr268 phosphorylation (∼2-fold) with no effects of CHO feeding (all P > 0.05). CHO increased exercise capacity where 90 g h-1 (233 ± 133 s) > 45 g h-1 (156 ± 66 s; P = 0.06) > 0 g h-1 (108 ± 54 s; P = 0.03). In conditions of high pre-exercise CHO availability, we conclude CHO feeding does not influence exercise-induced changes in LD morphology, glycogen utilisation or cell signalling pathways with regulatory roles in mitochondrial biogenesis.

Graded reductions in pre-exercise glycogen concentration do not augment exercise-induced nuclear AMPK and PGC-1α protein content in human muscle.

NEW FINDINGS: What is the central question of this study? What is the absolute level of pre-exercise glycogen concentration required to augment the exercise-induced signalling response regulating mitochondrial biogenesis? What is the main finding and its importance? Commencing high-intensity endurance exercise with reduced pre-exercise muscle glycogen concentrations confers no additional benefit to the early signalling responses that regulate mitochondrial biogenesis. ABSTRACT: We examined the effects of graded muscle glycogen on the subcellular location and protein content of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and mRNA expression of genes associated with the regulation of mitochondrial biogenesis and substrate utilisation in human skeletal muscle. In a repeated measures design, eight trained male cyclists completed acute high-intensity interval (HIT) cycling (8 × 5 min at 80% peak power output) with graded concentrations of pre-exercise muscle glycogen. Following initial glycogen-depleting exercise, subjects ingested  2 g kg-1  (L-CHO), 6 g kg-1 (M-CHO) or 14 g kg-1 (H-CHO) of carbohydrate during a 36 h period, such that exercise was commenced with graded (P < 0.05) muscle glycogen concentrations (mmol (kg dw)-1 : H-CHO, 531 ± 83; M-CHO, 332 ± 88; L-CHO, 208 ± 79). Exercise depleted muscle glycogen to <300 mmol (kg dw)-1 in all trials (mmol (kg dw)-1 : H-CHO, 270 ± 88; M-CHO, 173 ± 74; L-CHO, 100 ± 42) and induced comparable increases in nuclear AMPK protein content (∼2-fold) and PGC-1α (∼5-fold), p53 (∼1.5-fold) and carnitine palmitoyltransferase 1 (∼2-fold) mRNA between trials (all P < 0.05). The magnitude of increase in PGC-1α mRNA was also positively correlated with post-exercise glycogen concentration (P < 0.05). In contrast, neither exercise nor carbohydrate availability affected the subcellular location of PGC-1α protein or PPAR, SCO2, SIRT1, DRP1, MFN2 or CD36 mRNA. Using a sleep-low, train-low model with a high-intensity endurance exercise stimulus, we conclude that pre-exercise muscle glycogen does not modulate skeletal muscle cell signalling.

Analysis of the world record time for combined father and son marathon.

The aim of this study was to examine the physiological profiles and the pacing strategies of the father (59 yr old) and son (34 yr old) who broke the World Record time (4:59:22; father: 2:27:52, son: 2:31:30) for combined father and son marathon in 2019. Oxygen uptake (V̇o2), heart rate (HR), ventilation (V̇e), blood lactate concentration (La), and running economy (RE) were measured during treadmill-running tests. The total distance of the marathon was divided into eight sections of 5 km and one last section of 2.195 km, and the relative average running velocity on each section was calculated individually. V̇o2max, HRmax, V̇emax, and Lamax were 65.4 mL·kg-1·min-1, 165 beats/min, 115 L/min, 5.7 mmol/L for the father and 66.9 mL·kg-1·min-1, 181 beats/min, 153 L/min, 11.5 mmol/L for the son, respectively. At 17 km/h, RE was 210 mL·kg-1·km-1 for the father and 200 mL·kg-1·km-1 for the son, and % V̇o2max sustained was 90.9% for the father and 84.5% for the son, respectively. The father maintained an even running velocity during the marathon (running velocity CV <1%), while the son ran the second half-marathon 7% slower than the first one, and his running velocity markedly dropped from the 35th kilometer. Father and son who broke the World record time for combined father and son marathon had a similar level of performance, but their physiological profiles and pacing strategies during the marathon were different. A more even speed for the son could help them to improve their own record in the near future.NEW & NOTEWORTHY We provide novel data demonstrating that different physiological profiles can lead to the same level of performance in a marathon, even at different ages. The novelty of our study is that we report on the physiological characteristics, training routine, and in-race pacing strategy that allowed a father (59 yr old) and son (34 yr old) to break the World Record time for combined father and son marathon. The father also established a new World record marathon time for the age of 59.

Graded reductions in preexercise muscle glycogen impair exercise capacity but do not augment skeletal muscle cell signaling: implications for CHO periodization.

We examined the effects of graded muscle glycogen on exercise capacity and modulation of skeletal muscle signaling pathways associated with the regulation of mitochondrial biogenesis. In a repeated-measures design, eight men completed a sleep-low, train-low model comprising an evening glycogen-depleting cycling protocol followed by an exhaustive exercise capacity test [8 × 3 min at 80% peak power output (PPO), followed by 1-min efforts at 80% PPO until exhaustion] the subsequent morning. After glycogen-depleting exercise, subjects ingested a total of 0 g/kg (L-CHO), 3.6 g/kg (M-CHO), or 7.6 g/kg (H-CHO) of carbohydrate (CHO) during a 6-h period before sleeping, such that exercise was commenced the next morning with graded (P < 0.05) muscle glycogen concentrations (means ± SD: L-CHO: 88 ± 43, M-CHO: 185 ± 62, H-CHO: 278 ± 47 mmol/kg dry wt). Despite differences (P < 0.05) in exercise capacity at 80% PPO between trials (L-CHO: 18 ± 7, M-CHO: 36 ± 3, H-CHO: 44 ± 9 min), exercise induced comparable AMPKThr172 phosphorylation (~4-fold) and PGC-1α mRNA expression (~5-fold) after exercise and 3 h after exercise, respectively. In contrast, neither exercise nor CHO availability affected the phosphorylation of p38MAPKThr180/Tyr182 or CaMKIIThr268 or mRNA expression of p53, Tfam, CPT-1, CD36, or PDK4. Data demonstrate that when exercise is commenced with muscle glycogen < 300 mmol/kg dry wt, further graded reductions of 100 mmol/kg dry weight impair exercise capacity but do not augment skeletal muscle cell signaling. NEW & NOTEWORTHY We provide novel data demonstrating that when exercise is commenced with muscle glycogen below 300 mmol/kg dry wt (as achieved with the sleep-low, train-low model) further graded reductions in preexercise muscle glycogen of 100 mmol/kg dry wt reduce exercise capacity at 80% peak power output by 20-50% but do not augment skeletal muscle cell signaling.