Trehalose Improved 20-min Cycling Time-Trial Performance After 100-min Cycling in Amateur Cyclists.

Carbohydrate (CHO) supplementation during endurance exercise can improve performance. However, it is unclear whether low glycemic index (GI) CHO leads to differential ergogenic and metabolic effects compared with a standard high GI CHO. This study investigated the ergogenic and metabolic effects of CHO supplementation with distinct GIs, namely, (a) trehalose (30 g/hr), (b) isomaltulose (30 g/hr), (c) maltodextrin (60 g/hr), and (d) placebo (water). In this double-blind, crossover, counterbalanced, placebo-controlled study, 13 male cyclists cycled a total of 100 min at varied exercise intensity (i.e., 10-min stages at 1.5, 2.0, and 2.5 W/kg; repeated three times plus two 5-min stages at 1.0 W/kg before and after the protocol), followed by a 20-min time trial on four separated occasions. Blood glucose and lactate (every 20 min), heart rate, and ratings of perceived exertion were collected throughout, and muscle biopsies were taken before and immediately after exercise. The results showed that trehalose improved time-trial performance compared with placebo (total work done 302 ± 39 vs. 287 ± 48 kJ; p = .01), with no other differences between sessions (all p ≥ .07). Throughout the 100-min protocol, blood glucose was higher with maltodextrin compared with the other supplements at all time points (all p < .05). Heart rate, ratings of perceived exertion, muscle glycogen content, blood glucose, and lactate were not different between conditions when considering the 20-min time trial (all p > .05). Trehalose supplementation throughout endurance exercise improved cycling performance and appears to be an appropriate CHO source for exercise tasks up to 2 hr. No ergogenic superiority between the different types of CHO was established.

Carbohydrate intake before and during high intensity exercise with reduced muscle glycogen availability affects the speed of muscle reoxygenation and performance.

Muscle glycogen state and carbohydrate (CHO) supplementation before and during exercise may impact responses to high-intensity interval training (HIIT). This study determined cardiorespiratory, substrate metabolism, muscle oxygenation, and performance when completing HIIT with or without CHO supplementation in a muscle glycogen depleted state. On two occasions, in a cross-over design, eight male cyclists performed a glycogen depletion protocol prior to HIIT during which either a 6% CHO drink (60 g.hr-1) or placebo (%CHO, PLA) was consumed. HIIT consisted of 5 × 2 min at 80% peak power output (PPO), 3 × 10-min bouts of steady-state (SS) cycling (50, 55, 60% PPO), and a time-to-exhaustion (TTE) test. There was no difference in SS [Formula: see text], HR, substrate oxidation and gross efficiency (GE %) between CHO and PLA conditions. A faster rate of muscle reoxygenation (%. s-1) existed in PLA after the 1st (Δ - 0.23 ± 0.22, d = 0.58, P < 0.05) and 3rd HIIT intervals (Δ - 0.34 ± 0.25, d = 1.02, P < 0.05). TTE was greater in CHO (7.1 ± 5.4 min) than PLA (2.5 ± 2.3 min, d = 0.98, P < 0.05). CHO consumption before and during exercise under reduced muscle glycogen conditions did not suppress fat oxidation, suggesting a strong regulatory role of muscle glycogen on substrate metabolism. However, CHO ingestion provided a performance benefit under intense exercise conditions commenced with reduced muscle glycogen. More research is needed to understand the significance of altered muscle oxygenation patterns during exercise.

Fluoride as a Potential Repressor of Glycogen Metabolism in Skeletal Muscle Cell Line CCL136.

The exposure of humans to fluorine is connected with its presence in the air, food and water. It is well known that fluorides even at a low concentration but with long time exposure accumulate in the body and lead to numerous metabolic disorders. Fluoride is recognised as a factor modulating the energy metabolism of cells. This interaction is of particular importance in muscle cells, which are cells with high metabolic activity related to the metabolism of glucose and glycogen. In someone suffering from chronic fluoride poisoning, frequent symptoms are chronic fatigue not relieved by extra sleep or rest, muscular weakness, muscle spasms, involuntary twitching. The aim of this study was to examine the effect of fluorine at concentrations determined in blood of people environmentally exposed to fluorides on activity and expression of enzymes taking part in metabolism of muscle glycogen. CCL136 cells were cultured under standard conditions with the addition of NaF. The amount of ATP produced by the cells was determined using the HPLC method, the amount and expression of genes responsible for glycogen metabolism using WB and RT PCR methods and the amount of glycogen in cells using the fluorimetric and PAS methods. It has been shown that in CCL136 cells exposed to 1, 3 and 10 µM NaF there is a change in the energy state and expression pattern of enzymes involved in the synthesis and breakdown of glycogen. It was observed that NaF caused a decrease in ATP content in CCL136 cells. Fluoride exposure also increased glycogen deposition. These changes were accompanied by a decrease in gene expression and the level of enzymatic proteins related to glycogen metabolism: glycogen synthase, glycogen synthase kinase and glycogen phosphorylase. The results obtained shed new light on the molecular mechanisms by which fluoride acts as an environmental toxin.

Muscle metabolism and impaired sprint performance in an elite women's football game.

The present study examined skeletal muscle metabolism and changes in repeated sprint performance during match play for n = 20 competitive elite women outfield players. We obtained musculus vastus lateralis biopsies and blood samples before, after, and following intense periods in each half of a friendly match, along with 5 × 30-meter sprint tests and movement pattern analyses (10-Hz S5 Global Positioning System [GPS]). Muscle glycogen decreased by 39% and 42% after an intense period of the second half and after the match, respectively, compared to baseline (p < 0.05). Post-match, 80% type I fibers and 69% type II fibers were almost empty or completely empty of glycogen. Muscle lactate was higher (p < 0.05) after the intense period of the first half and post-match compared to baseline (14.3 ± 4.6 (±SEM) and 12.9 ± 5.7 vs. 6.4 ± 3.7 mmol/kg d.w.). Muscle phosphocreatine was reduced (p < 0.05) by 16% and 12%, respectively, after an intense period in the first and second half compared to baseline. Blood lactate and glucose increased during the match and peaked at 8.4 ± 2.0 and 7.9 ± 1.2 mmol/L, respectively. Mean 5 × 30 m sprint time declined by 3.2 ± 1.7 and 7.0 ± 2.1% after the first and second half, respectively, and 4.7 ± 1.6% (p < 0.05) after an intense period in the first half compared to baseline. In conclusion, match play in elite female football players resulted in marked glycogen depletion in both fiber types, which may explain fatigue at the end of a match. Repeated sprint ability was impaired after intense periods in the first half and after both halves, which may be associated with the observed muscle metabolite perturbations.

Acute arm and leg muscle glycogen and metabolite responses to small-sided football games in healthy young men.

PURPOSE: Studies have indicated upper body involvement during football, provoking long-term muscular adaptations. This study aimed at examining the acute metabolic response in upper and lower body skeletal muscle to football training organized as small-sided games (SSG). METHODS: Ten healthy male recreational football players [age 24 ± 1 (± SD) yrs; height 183 ± 4 cm; body mass 83.1 ± 9.7 kg; body fat 15.5 ± 5.4%] completed 1-h 5v5 SSG (4 × 12 min interspersed with 4-min recovery periods). Muscle biopsies were obtained from m. vastus lateralis (VL) and m. deltoideus (DE) pre- and post-SSG for muscle glycogen and metabolite analyses. Blood lactate samples were obtained at rest, middle and end of the SSG. RESULTS: Muscle glycogen in VL decreased (P < 0.01) by 21% and tended (P = 0.08) to decrease in DE by 13%. Muscle lactate increased in VL (117%; P < 0.001) and DE (81%; P < 0.001) during the game, while blood lactate rose threefold. Muscle ATP and PCr were unaltered, but intermuscular differences were detected for ATP at both time points (P < 0.001) and for PCr at pre-SSG (P < 0.05) with VL demonstrating higher values than DE, while muscle creatine rose in VL (P < 0.001) by 41% and by 22% in DE (P = 0.02). Baseline citrate synthase maximal activity was higher (P < 0.05) in VL compared to DE, whereas baseline muscle lactate concentration was higher (P < 0.05) in DE than VL. CONCLUSION: The upper body may be extensively involved during football play, but besides a rise in muscle lactate in the deltoideus muscle similar to the leg muscles, the present study did not demonstrate acute metabolic changes of an order that may explain the previously reported training effect of football play in the upper extremities.

Exercise twice-a-day potentiates markers of mitochondrial biogenesis in men.

Endurance exercise begun with reduced muscle glycogen stores seems to potentiate skeletal muscle protein abundance and gene expression. However, it is unknown whether this greater signaling responses is due to performing two exercise sessions in close proximity-as a first exercise session is necessary to reduce the muscle glycogen stores. In the present study, we manipulated the recovery duration between a first muscle glycogen-depleting exercise and a second exercise session, such that the second exercise session started with reduced muscle glycogen in both approaches but was performed either 2 or 15 hours after the first exercise session (so-called "twice-a-day" and "once-daily" approaches, respectively). We found that exercise twice-a-day increased the nuclear abundance of transcription factor EB (TFEB) and nuclear factor of activated T cells (NFAT) and potentiated the transcription of peroxisome proliferator-activated receptor-É£ coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor-alpha (PPARα), and peroxisome proliferator-activated receptor beta/delta (PPARß/δ) genes, in comparison with the once-daily exercise. These results suggest that part of the elevated molecular signaling reported with previous "train-low" approaches might be attributed to performing two exercise sessions in close proximity. The twice-a-day approach might be an effective strategy to induce adaptations related to mitochondrial biogenesis and fat oxidation.

Phenotype and genotype of 197 British patients with McArdle disease: An observational single-centre study.

McArdle disease is caused by recessive mutations in PYGM gene. The condition is considered to cause a "pure" muscle phenotype with symptoms including exercise intolerance, inability to perform isometric activities, contracture, and acute rhabdomyolysis leading to acute renal failure. This is a retrospective observational study aiming to describe phenotypic and genotypic features of a large cohort of patients with McArdle disease between 2011 and 2019. Data relating to genotype and phenotype, including frequency of rhabdomyolysis, fixed muscle weakness, gout and comorbidities, inclusive of retinal disease (pattern retinal dystrophy) and thyroid disease, were collected. Data from 197 patients are presented. Seven previously unpublished PYGM mutations are described. Exercise intolerance (100%) and episodic rhabdomyolysis (75.6%) were the most common symptoms. Fixed muscle weakness was present in 82 (41.6%) subjects. Unexpectedly, ptosis was observed in 28 patients (14.2%). Hyperuricaemia was a common finding present in 88 subjects (44.7%), complicated by gout in 25% of cases. Thyroid dysfunction was described in 30 subjects (15.2%), and in 3 cases, papillary thyroid cancer was observed. Pattern retinal dystrophy was detected in 15 out of the 41 subjects that underwent an ophthalmic assessment (36.6%). In addition to fixed muscle weakness, ptosis was a relatively common finding. Surprisingly, dysfunction of thyroid and retinal abnormalities were relatively frequent comorbidities. Further studies are needed to better clarify this association, although our finding may have important implication for patient management.

Variation of skeletal muscle ultrasound imaging intensity in horses after treadmill exercise: a proof of concept for glycogen content estimation.

BACKGROUND: Glycogen in skeletal muscle is a major source of energy during exercise and an important determinant of endurance capacity, so that its measurement may provide a meaningful marker of athletes' preparation and a possible predictor of performance, both in humans and in equines. Gold standard of glycogen concentration measurement is the histochemical and biochemical analysis of biopsy-derived muscle tissue, an invasive and potentially injuring procedure. Recently, high-frequency ultrasound (US) technology is being exploited in human sports medicine to estimate muscle glycogen content. Therefore, aim of the present study is to evaluate the feasibility of US assessment of muscle glycogen in equines. RESULTS: US images of gluteus medius (GL) and semitendinosus (ST) muscles were obtained on eight healthy horses (3-10 years) before and after a steady-state exercise on treadmill (velocity: 4.0-12.5 m/s; duration: 2-20 min; heart rate: 137-218 b/min). Average image greyscale intensity was significantly different between GL and ST, both before and after exercise (p < 0.001). Comparing baseline and post-exercise US images, significant increase in greyscale intensity has been observed in ST (p < 0.001), but not in GL (p = 0.129). The volume of the exercise was significantly correlated with exercise-dependent change in image intensity (R2 = 0.891), consistent with a reduction of glycogen muscle stores resulting from aerobic activity. CONCLUSIONS: US technique evidences also in horses muscle changes possibly associated to glycogen utilisation during exercise. Present results on a small sample need to be further confirmed and provide preliminary data warranting future validation by direct glycogen measurement through biopsy technique.

The effects of exercise training versus intensive insulin treatment on skeletal muscle fibre content in type 1 diabetes mellitus rodents.

BACKGROUND: Intensive-insulin treatment (IIT) strategy for patients with type 1 diabetes mellitus (T1DM) has been associated with sedentary behaviour and the development of insulin resistance. Exercising patients with T1DM often utilize a conventional insulin treatment (CIT) strategy leading to increased insulin sensitivity through improved intramyocellular lipid (IMCL) content. It is unclear how these exercise-related metabolic adaptations in response to exercise training relate to individual fibre-type transitions, and whether these alterations are evident between different insulin strategies (CIT vs. IIT). PURPOSE: This study examined glycogen and fat content in skeletal muscle fibres of diabetic rats following exercise-training. METHODS: Male Sprague-Dawley rats were divided into four groups: Control-Sedentary, CIT- and IIT-treated diabetic sedentary, and CIT-exercised trained (aerobic/resistance; DARE). After 12 weeks, muscle-fibre lipids and glycogen were compared through immunohistochemical analysis. RESULTS: The primary findings were that both IIT and DARE led to significant increases in type I fibres when compared to CIT, while DARE led to significantly increased lipid content in type I fibres compared to IIT. CONCLUSIONS: These findings indicate that alterations in lipid content with insulin treatment and DARE are primarily evident in type I fibres, suggesting that muscle lipotoxicity in type 1 diabetes is muscle fibre-type dependant.

Carbohydrate restriction following strenuous glycogen-depleting exercise does not potentiate the acute molecular response associated with mitochondrial biogenesis in human skeletal muscle.

PURPOSE: Carbohydrate (CHO) restriction could be a potent metabolic regulator of endurance exercise-induced muscle adaptations. Here, we determined whether post-exercise CHO restriction following strenuous exercise combining continuous cycling exercise (CCE) and sprint interval exercise could affect the gene expression related to mitochondrial biogenesis and oxidative metabolism in human skeletal muscle. METHODS: In a randomized cross-over design, 8 recreationally active males performed two cycling exercise sessions separated by 4 weeks. Each session consisted of 60-min CCE and six 30-s all-out sprints, which was followed by ingestion of either a CHO or placebo beverage in the post-exercise recovery period. Muscle glycogen concentration and the mRNA levels of several genes related to mitochondrial biogenesis and oxidative metabolism were determined before, immediately after, and at 3 h after exercise. RESULTS: Compared to pre-exercise, strenuous cycling led to a severe muscle glycogen depletion (> 90%) and induced a large increase in PGC1A and PDK4 mRNA levels (~ 20-fold and ~ 10-fold, respectively) during the acute recovery period in both trials. The abundance of the other transcripts was not changed or was only moderately increased during this period. CHO restriction during the 3-h post-exercise period blunted muscle glycogen resynthesis but did not increase the mRNA levels of genes associated with muscle adaptation to endurance exercise, as compared with abundant post-exercise CHO consumption. CONCLUSION: CHO restriction after a glycogen-depleting and metabolically-demanding cycling session is not effective for increasing the acute mRNA levels of genes involved in mitochondrial biogenesis and oxidative metabolism in human skeletal muscle.

Achieving energy balance with a high-fat meal does not enhance skeletal muscle adaptation and impairs glycaemic response in a sleep-low training model.

NEW FINDINGS: What is the central question of this study? Does achieving energy balance mainly with ingested fat in a 'sleep-low' model of training with low muscle glycogen affect the early training adaptive response during recovery? What is the main finding and its importance? Replenishing the energy expended during exercise mainly from ingested fat to achieve energy balance in a 'sleep-low' model does not enhance the response of skeletal muscle markers of early adaptation to training and impairs glycaemic control the morning after compared to training with low energy availability. These findings are important for optimizing post-training dietary recommendations in relation to energy balance and macronutrient intake. ABSTRACT: Training with low carbohydrate availability (LCHO) has been shown to acutely enhance endurance training skeletal muscle response, but the concomitant energy deficit (ED) in LCHO interventions has represented a confounding factor in past research. This study aimed at determining if achieving energy balance with high fat (EB-HF) acutely enhances the adaptive response in LCHO compared to ED with low fat (ED-LF). In a crossover design, nine well-trained males completed a 'sleep-low' protocol: on day 1 they cycled to deplete muscle glycogen while reaching a set energy expenditure (30 kcal (kg of fat free mass (FFM))-1 ). Post-exercise, low carbohydrate, protein-matched meals completely (EB-HF, 30 kcal (kg FFM)-1 ) or partially (ED-LF, 9 kcal (kg FFM)-1 ) replaced the energy expended, with the majority of energy derived from fat in EB-HF. In the morning of day 2, participants exercised fasted, and skeletal muscle and blood samples were collected and a carbohydrate-protein drink was ingested at 0.5 h recovery. Muscle glycogen showed no treatment effect (P < 0.001) and decreased from 350 ± 98 to 192 ± 94 mmol (kg dry mass)-1 between rest and 0.5 h recovery. Phosphorylation status of the mechanistic target of rapamycin and AMP-activated protein kinase pathway proteins showed only time effects. mRNA expression of p53 increased after exercise (P = 0.005) and was higher in ED-LF at 3.5 h compared to EB-HF (P = 0.027). Plasma glucose and insulin area under the curve (P < 0.04) and peak values (P ≤ 0.05) were higher in EB-HF after the recovery drink. Achieving energy balance with a high-fat meal in a 'train-low' ('sleep-low') model did not enhance markers of skeletal muscle adaptation and impaired glycaemia in response to a recovery drink following training in the morning.

A 3-day dietary manipulation affects muscle glycogen and results in modifications of carbohydrate and fat metabolism during exercise when hyperglycaemic.

PURPOSE: The effect of hyperglycaemia on exercise with low and elevated muscle glycogen on glucose utilization (GUR), carbohydrate and fat oxidation, hormonal and metabolite responses, as well as rating of perceived exertion (RPE) were explored. METHODS: Five healthy trained males were exercised for 90 min at 70% V̇O2max in two trials, while glucose was infused intravenously at rates to "clamp" blood glucose at 12 mM. On one occasion, participants were 'loaded' with carbohydrate (CHO-L), whilst on a separate occasion, participants were glycogen depleted (CHO-D). Prior exercise and dietary manipulations produced the 'loaded' and 'depleted' states. RESULTS: The CHO-L and CHO-D conditions resulted in muscle glycogen concentrations of 377 and 159 mmol/g dw, respectively. Hyperglycaemia elevated plasma insulin concentrations with higher levels for CHO-L than for CHO-D (P < 0.01). Conversely, CHO-D elevated plasma adrenaline and noradrenaline higher than CHO-L (P < 0.05). Plasma fat metabolites (NEFA, ß-hydroxybutyrate, and glycerol) were higher under CHO-D than CHO-L (P < 0.01). The resultant was that the rates of total carbohydrate and fat oxidation were elevated and depressed for loaded CHO-L vs CHO-D respectively (P < 0.01), although no difference was found for GUR (P > 0.05). The RPE over the exercise period was higher for CHO-D than CHO-L (P < 0.05). CONCLUSION: Hyperglycaemia during exercise, when muscle glycogen is reduced, attenuates insulin but promotes catecholamines and fat metabolites. The effect is a subsequent elevation of fat oxidation, a reduction in CHO oxidation without a concomitant increase in GUR, and an increase in RPE.

Hyperinsulinaemia and hyperglycaemia promote glucose utilization and storage during low- and high-intensity exercise.

PURPOSE: The effect of hyperglycaemia with and without additional insulin was explored at a low and high intensity of exercise (40% vs 70% VO2peak) on glucose utilization (GUR), carbohydrate oxidation, non-oxidative glucose disposal (NOGD), and muscle glycogen. METHODS: Eight healthy trained males were exercised for 120 min in four trials, twice at 40% VO2peak and twice at 70% VO2peak, while glucose was infused intravenously (40%G; 70%G) at rates to "clamp" blood glucose at 10 mM. On one occasion at each exercise intensity, insulin was also infused at 40 mU/m2/per min (i.e. 40%GI and 70%GI). The glucose and insulin infusion began 30 min prior to exercise and throughout exercise. A muscle biopsy was taken at the end of exercise for glycogen analysis. RESULTS: Hyperglycaemia significantly elevated plasma insulin concentration (p < 0.001), although no difference was observed between the exercise intensities. Insulin infusion during both mild and severe exercise resulted in increased insulin concentrations (p < 0.01) and GUR (p < 0.01) compared with glucose (40%GI by 25.2%; 70%GI by 26.2%), but failed to significantly affect carbohydrate, fat and protein oxidation. NOGD was significantly higher for GI trials at both intensities (p < 0.05) with storage occurring during both lower intensities (62.7 ± 19.6 g 40%GI; 127 ± 20.7 g 40%GI) and 70%GI (29.0 ± 20.0 g). Muscle glycogen concentrations were significantly depleted from rest (p < 0.01) after all four trials. CONCLUSION: Hyperinsulinaemia in the presence of hyperglycaemia during both low- and high-intensity exercise promotes GUR and NOGD, but does not significantly affect substrate oxidation.

Liver and muscle glycogen oxidation and performance with dose variation of glucose-fructose ingestion during prolonged (3 h) exercise.

PURPOSE: This study investigated the effect of small manipulations in carbohydrate (CHO) dose on exogenous and endogenous (liver and muscle) fuel selection during exercise. METHOD: Eleven trained males cycled in a double-blind randomised order on 4 occasions at 60% [Formula: see text] for 3 h, followed by a 30-min time-trial whilst ingesting either 80 g h-1 or 90 g h-1 or 100 g h-1 13C-glucose-13C-fructose [2:1] or placebo. CHO doses met, were marginally lower, or above previously reported intestinal saturation for glucose-fructose (90 g h-1). Indirect calorimetry and stable mass isotope [13C] techniques were utilised to determine fuel use. RESULT: Time-trial performance was 86.5 to 93%, 'likely, probable' improved with 90 g h-1 compared 80 and 100 g h-1. Exogenous CHO oxidation in the final hour was 9.8-10.0% higher with 100 g h-1 compared with 80 and 90 g h-1 (ES = 0.64-0.70, 95% CI 9.6, 1.4 to 17.7 and 8.2, 2.1 to 18.6). However, increasing CHO dose (100 g h-1) increased muscle glycogen use (101.6 ± 16.6 g, ES = 0.60, 16.1, 0.9 to 31.4) and its relative contribution to energy expenditure (5.6 ± 8.4%, ES = 0.72, 5.6, 1.5 to 9.8 g) compared with 90 g h-1. Absolute and relative muscle glycogen oxidation between 80 and 90 g h-1 were similar (ES = 0.23 and 0.38) though a small absolute (85.4 ± 29.3 g, 6.2, - 23.5 to 11.1) and relative (34.9 ± 9.1 g, - 3.5, - 9.6 to 2.6) reduction was seen in 90 g h-1 compared with 100 g h-1. Liver glycogen oxidation was not significantly different between conditions (ES < 0.42). Total fat oxidation during the 3-h ride was similar in CHO conditions (ES < 0.28) but suppressed compared with placebo (ES = 1.05-1.51). CONCLUSION: 'Overdosing' intestinal transport for glucose-fructose appears to increase muscle glycogen reliance and negatively impact subsequent TT performance.

Missense mutations have unexpected consequences: The McArdle disease paradigm.

McArdle disease is a disorder of muscle glycogen metabolism caused by mutations in the PYGM gene, encoding for the muscle-specific isoform of glycogen phosphorylase (M-GP). The activity of this enzyme is completely lost in patients' muscle biopsies, when measured with a standard biochemical test which, does not allow to determine M-GP protein levels. We aimed to determine M-GP protein levels in the muscle of McArdle patients, by studying biopsies of 40 patients harboring a broad spectrum of PYGM mutations and 22 controls. Lack of M-GP protein was found in muscle in the vast majority (95%) of patients, irrespective of the PYGM genotype, including those carrying missense mutations, with few exceptions. M-GP protein biosynthesis is not being produced by PYGM mutations inducing premature termination codons (PTC), neither by most PYGM missense mutations. These findings explain the lack of PYGM genotype-phenotype correlation and have important implications for the design of molecular-based therapeutic approaches.

Identification of genomic regions and candidate genes for chicken meat ultimate pH by combined detection of selection signatures and QTL.

BACKGROUND: The understanding of the biological determinism of meat ultimate pH, which is strongly related to muscle glycogen content, is a key point for the control of muscle integrity and meat quality in poultry. In the present study, we took advantage of a unique model of two broiler lines divergently selected for the ultimate pH of the pectoralis major muscle (PM-pHu) in order to decipher the genetic control of this trait. Two complementary approaches were used: detection of selection signatures generated during the first five generations and genome-wide association study for PM-pHu and Sartorius muscle pHu (SART-pHu) at the sixth generation of selection. RESULTS: Sixty-three genomic regions showed significant signatures of positive selection. Out of the 10 most significant regions (detected by HapFLK or FLK method with a p-value below 1e-6), 4 were detected as soon as the first generation (G1) and were recovered at each of the four following ones (G2-G5). Another four corresponded to a later onset of selection as they were detected only at G5. In total, 33 SNPs, located in 24 QTL regions, were significantly associated with PM-pHu. For SART-pHu, we detected 18 SNPs located in 10 different regions. These results confirmed a polygenic determinism for these traits and highlighted two major QTL: one for PM-pHu on GGA1 (with a Bayes Factor (BF) of 300) and one for SART-pHu on GGA4 (with a BF of 257). Although selection signatures were enriched in QTL for PM-pHu, several QTL with strong effect haven't yet responded to selection, suggesting that the divergence between lines might be further increased. CONCLUSIONS: A few regions of major interest with significant selection signatures and/or strong association with PM-pHu or SART-pHu were evidenced for the first time in chicken. Their gene content suggests several candidates associated with diseases of glycogen storage in humans. The impact of these candidate genes on meat quality and muscle integrity should be further investigated in chicken.

Ergogenic properties of metformin in simulated high altitude.

Metformin augments glucose/glycogen regulation and may acutely promote fatigue resistance during high-intensity exercise. In hypobaric environments, such as high altitude, the important contribution of carbohydrates to physiological function is accentuated as glucose/glycogen dependence is increased. Because hypoxia/hypobaria decreases insulin sensitivity, replenishing skeletal muscle glycogen in high altitude becomes challenging and subsequent physical performance may be compromised. We hypothesized that in conditions where glycogen repletion was critical to physical outcomes, metformin would attenuate hypoxia-mediated decrements in exercise performance. On three separate randomly ordered occasions, 13 healthy men performed glycogen-depleting exercise and ingested a low-carbohydrate dinner (1200 kcals, <10% carbohydrate). The next morning, in either normoxia or hypoxia (FiO2 =0.15), they ingested a high-carbohydrate breakfast (1225 kcals, 70% carbohydrate). Placebo (719 mg maltodextrin) or metformin (500 mg BID) was consumed 3 days prior to each hypoxia visit. Subjects completed a 12.5 km cycle ergometer time trial 3.5 hours following breakfast. Hypoxia decreased resting and exercise oxyhemoglobin saturation (P<.001). Neither hypoxia nor metformin affected the glucose response to breakfast (P=.977), however, compared with placebo, metformin lowered insulin concentration in hypoxia 45 minutes after breakfast (64.1±6.6 µU/mL vs 48.5±7.8 µU/mL; mean±SE; P<.001). Post-breakfast, pre-exercise vastus lateralis glycogen content increased in normoxia (+33%: P=.025) and in hypoxia with metformin (+81%; P=.006), but not in hypoxia with placebo (+27%; P=.167). Hypoxia decreased time trial performance compared with normoxia (P<.01). This decrement was similar with placebo (+2.6±0.8 minutes) and metformin (+1.6±0.3 minutes). These results indicate that metformin promotes glycogen synthesis but not endurance exercise performance in healthy men exposed to simulated high altitude.

Relationship between motor corticospinal excitability and ventilatory response during intense exercise.

PURPOSE: Effort sense has been suggested to be involved in the hyperventilatory response during intense exercise (IE). However, the mechanism by which effort sense induces an increase in ventilation during IE has not been fully elucidated. The aim of this study was to determine the relationship between effort-mediated ventilatory response and corticospinal excitability of lower limb muscle during IE. METHODS: Eight subjects performed 3 min of cycling exercise at 75-85 % of maximum workload twice (IE1st and IE2nd). IE2nd was performed after 60 min of resting recovery following 45 min of submaximal cycling exercise at the workload corresponding to ventilatory threshold. Vastus lateralis muscle response to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs), effort sense of legs (ESL, Borg 0-10 scale), and ventilatory response were measured during the two IEs. RESULTS: The slope of ventilation (l/min) against CO2 output (l/min) during IE2nd (28.0 ± 5.6) was significantly greater than that (25.1 ± 5.5) during IE1st. Mean ESL during IE was significantly higher in IE2nd (5.25 ± 0.89) than in IE1st (4.67 ± 0.62). Mean MEP (normalized to maximal M-wave) during IE was significantly lower in IE2nd (66 ± 22 %) than in IE1st (77 ± 24 %). The difference in mean ESL between the two IEs was significantly (p < 0.05, r = -0.82) correlated with the difference in mean MEP between the two IEs. CONCLUSIONS: The findings suggest that effort-mediated hyperventilatory response to IE may be associated with a decrease in corticospinal excitability of exercising muscle.

¹³C MRS reveals a small diurnal variation in the glycogen content of human thigh muscle.

There is marked diurnal variation in the glycogen content of skeletal muscles of animals, but few studies have addressed such variations in human muscles. (13)C MRS can be used to noninvasively measure the glycogen content of human skeletal muscle, but no study has explored the diurnal variations in this parameter. This study aimed to investigate whether a diurnal variation in glycogen content occurs in human muscles and, if so, to what extent it can be identified using (13)C MRS. Six male volunteers were instructed to maintain their normal diet and not to perform strenuous exercise for at least 3 days before and during the experiment. Muscle glycogen and blood glucose concentrations were measured six times in 24 h under normal conditions in these subjects. The glycogen content in the thigh muscle was determined noninvasively by natural abundance (13)C MRS using a clinical MR system at 3 T. Nutritional analysis revealed that the subjects' mean carbohydrate intake was 463 ± 137 g, being approximately 6.8 ± 2.4 g/kg body weight. The average sleeping time was 5.9 ± 1.0 h. The glycogen content in the thigh muscle at the starting point was 64.8 ± 20.6 mM. Although absolute and relative individual variations in muscle glycogen content were 7.0 ± 2.1 mM and 11.3 ± 4.6%, respectively, no significant difference in glycogen content was observed among the different time points. This study demonstrates that normal food intake (not fat and/or carbohydrate rich), sleep and other daily activities have a negligible influence on thigh muscle glycogen content, and that the diurnal variation of the glycogen content in human muscles is markedly smaller than that in animal muscles. Moreover, the present results also support the reproducibility and availability of (13)C MRS for the evaluation of the glycogen content in human muscles.

Hyperthermia, but not muscle water deficit, increases glycogen use during intense exercise.

We determined if dehydration alone or in combination with hyperthermia accelerates muscle glycogen use during intense exercise. Seven endurance-trained cyclists (VO2max = 54.4 ± 1.05 mL/kg/min) dehydrated 4.6% of body mass (BM) during exercise in the heat (150 min at 33 ± 1 °C, 25 ± 2% humidity). During recovery (4 h), subjects remained dehydrated (HYPO trial) or recovered all fluid losses (REH trials). Finally, subjects exercised intensely (75% VO2max ) for 40 min in a neutral (25 ± 1 °C; HYPO and REH trials) or in a hot environment (36 ± 1 °C; REHHOT ). Before the final exercise bout vastus lateralis glycogen concentration was similar in all three trials (434 ± 57 mmol/kg of dry muscle (dm)) but muscle water content was lower in the HYPO (357 ± 14 mL/100 g dm) than in REH trials (389 ± 25 and 386 ± 25 mL/100 g dm; P < 0.05). After 40 min of intense exercise, intestinal temperature was similar between the HYPO and REHHOT trials (39.2 ± 0.5 and 39.2 ± 0.4 °C, respectively) and glycogen use was similar (172 ± 86 and 185 ± 97 mmol/kg dm, respectively) despite large differences in muscle water content. In contrast, during REH, intestinal temperature (38.5 ± 0.4 °C) and glycogen use (117 ± 52 mmol/kg dm) were significantly lower than during HYPO and REHHOT . Our data suggest that hyperthermia stimulates glycogen use during intense exercise while muscle water deficit has a minor role.