Endurance-trained Athletes Research Articles

Intravenous Iron Does Not Augment the Hemoglobin Mass Response to Simulated Hypoxia.

Iron is integral for erythropoietic adaptation to hypoxia, yet the importance of supplementary iron compared with existing stores is poorly understood. The aim of the present study was to compare the magnitude of the hemoglobin mass (Hbmass) in response to altitude in athletes with intravenous (IV), oral, or placebo iron supplementation. Thirty-four, nonanemic, endurance-trained athletes completed 3 wk of simulated altitude (3000 m, 14 h·d), receiving two to three bolus iron injections (ferric carboxymaltose), daily oral iron supplementation (ferrous sulfate), or a placebo, commencing 2 wk before and throughout altitude exposure. Hbmass and markers of iron regulation were assessed at baseline (day -14), immediately before (day 0), weekly during (days 8 and 15), and immediately, 1, 3, and 6 wk after (days 22, 28, 42, and 63) the completion of altitude exposure. Hbmass significantly increased after altitude exposure in athletes with IV (mean % [90% confidence interval (CI)], 3.7% [2.8-4.7]) and oral (3.2% [2.2-4.2]) supplementation and remained elevated at 7 d postaltitude in oral (2.9% [1.5-4.3]) and 21 d after in IV (3.0% [1.5-4.6]) supplementation. Hbmass was not significantly higher than baseline at any time point in placebo. Iron supplementation appears necessary for optimal erythropoietic adaptation to altitude exposure. IV iron supplementation during 3 wk of simulated live high-train low altitude training offered no additional benefit in terms of the magnitude of the erythropoietic response for nonanemic endurance athletes compared with oral supplementation.

Dissociation of intramyocellular lipid storage and insulin resistance in trained athletes and type 2 diabetes patients; involvement of perilipin 5?

Intramyocellular lipid storage is negatively associated with insulin sensitivity. However, endurance trained athletes and type 2 diabetes mellitus (T2DM) patients store similar amounts of lipids in their muscle; the so-called athlete's paradox. Compared to T2DM, trained athletes possess higher levels of perilipin 5 (PLIN5), a lipid droplet (LD) coating protein. We examined whether coating LD with PLIN5 affects the pattern of muscle lipid (LD size and number) in relation to the athlete's paradox. Despite differences in PLIN5 protein content, we observed that coating the LD with PLIN5 could not explain the observed differences in LD size and number between athletes and T2DM. PLIN5-coated LDs were positively associated with oxidative capacity but not with insulin sensitivity. We conclude that coating of LDs with PLIN5 cannot causally explain the athlete's paradox. Intramyocellular lipid (IMCL) hampers insulin sensitivity, albeit not in endurance-trained athletes (Trained). Compared to type 2 diabetes mellitus (T2DM) patients, Trained subjects have high levels of perilipin 5 (PLIN5). In the present study, we tested whether the fraction of PLIN5-coated lipid droplets (LDs) is a determinant of skeletal muscle insulin sensitivity and contributes to the athlete's paradox. Muscle biopsies were taken from eight Trained, Lean sedentary, Obese and T2DM subjects. Trained, Obese and T2DM subjects were matched for total IMCL content. Confocal images were analysed for lipid area fraction, LD size and number and PLIN5+ and PLIN5- LDs were measured. A stepwise linear regression was performed to identify factors explaining observed variance in glucose infusion rate (GIR). Trained and T2DM subjects stored IMCL differently; Trained subjects had a higher number of LDs compared to T2DM subjects (0.037±0.004μm-2 vs. 0.023±0.003μm-2 , P=0.024) that were non-significantly smaller (0.27±0.01μm2 vs. 0.32±0.02μm2 , P=0.197, Trained vs. T2DM). Even though total PLIN5 protein content was almost double in Trained vs. T2DM subjects (1.65±0.21AU vs. 0.89±0.09AU, P=0.004), PLIN5 coating did not affect LD number or size significantly. Of the observed variance in GIR, the largest fraction by far (70.2%) was explained by maximal oxygen uptake. Adding PLIN5 protein content or PLIN5+ LDs increased the explained variance in GIR (74.7% and 80.7% for PLIN5 protein content and PLIN5+ LDs, respectively). Thus, the putative relationship between PLIN5 and insulin sensitivity is at best indirect and is apparent only in conjunction with maximal oxygen uptake. Hence, PLIN5 abundance cannot be causally linked to the athlete's paradox.

Influence of combined iron supplementation and simulated hypoxia on the haematological module of the athlete biological passport.

The integrity of the athlete biological passport (ABP) is underpinned by understanding normal fluctuations of its biomarkers to environmental or medical conditions, for example, altitude training or iron deficiency. The combined impact of altitude and iron supplementation on the ABP was evaluated in endurance-trained athletes (n=34) undertaking 3weeks of simulated live-high: train-low (14h.d-1 , 3000m). Athletes received either oral, intravenous (IV) or placebo iron supplementation, commencing 2weeks prior and continuing throughout hypoxic exposure. Venous blood was sampled twice prior, weekly during, and up to 6weeks after altitude. Individual ABP thresholds for haemoglobin concentration ([Hb]), reticulocyte percentage (%retic), and OFF score were calculated using the adaptive model and assessed at 99% and 99.9% specificity. Eleven athletes returned values outside of the calculated reference ranges at 99%, with 8 at 99.9%. The percentage of athletes exceeding the thresholds in each group was similar, but IV returned the most individual occurrences. A similar frequency of abnormalities occurred across the 3 biomarkers, with abnormal [Hb] and OFF score values arising mainly during-, and %retic values mainly post- altitude. Removing samples collected during altitude from the model resulted in 10 athletes returning abnormal values at 99% specificity, 2 of whom had not triggered the model previously. In summary, the abnormalities observed in response to iron supplementation and hypoxia were not systematic and mostly in line with expected physiological adaptations. They do not represent a uniform weakness in the ABP. Nevertheless, altitude training and iron supplementation should be carefully considered by experts evaluating abnormal ABP profiles.

Keto-adaptation enhances exercise performance and body composition responses to training in endurance athletes

BackgroundLow-carbohydrate diets have recently grown in popularity among endurance athletes, yet little is known about the long-term (>4wk) performance implications of consuming a low-carbohydrate high fat ketogenic diet (LCKD) in well-trained athletes. MethodsTwenty male endurance-trained athletes (age 33±11y, body mass 80±11kg; BMI 24.7±3.1kg/m2) who habitually consumed a carbohydrate-based diet, self-selected into a high-carbohydrate (HC) group (n=11, %carbohydrate:protein:fat=65:14:20), or a LCKD group (n=9, 6:17:77). Both groups performed the same training intervention (endurance, strength and high intensity interval training (HIIT)). Prior to and following successful completion of 12-weeks of diet and training, participants had their body composition assessed, and completed a 100km time trial (TT), six second (SS) sprint, and a critical power test (CPT). During post-intervention testing the HC group consumed 30–60g/h carbohydrate, whereas the LCKD group consumed water, and electrolytes. ResultsThe LCKD group experienced a significantly greater decrease in body mass (HC −0.8kg, LCKD −5.9kg; P=0.006, effect size (ES): 0.338) and percentage body fat percentage (HC −0.7%, LCKD −5.2%; P=0.008, ES: 0.346). Fasting serum beta-hydroxybutyrate (βHB) significantly increased from 0.1 at baseline to 0.5mmol/L in the LCKD group (P=0.011, ES: 0.403) in week 12. There was no significant change in performance of the 100km TT between groups (HC −1.13min·s, LCKD −4.07min·s, P=0.057, ES: 0.196). SS sprint peak power increased by 0.8 watts per kilogram bodyweight (w/kg) in the LCKD group, versus a −0.1w/kg reduction in the HC group (P=0.025, ES: 0.263). CPT peak power decreased by −0.7w/kg in the HC group, and increased by 1.4w/kg in the LCKD group (P=0.047, ES: 0.212). Fat oxidation in the LCKD group was significantly greater throughout the 100km TT. ConclusionsCompared to a HC comparison group, a 12-week period of keto-adaptation and exercise training, enhanced body composition, fat oxidation during exercise, and specific measures of performance relevant to competitive endurance athletes.

Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal

ObjectiveWe tested the hypothesis that skeletal muscle of endurance-trained male runners would exhibit elevated autophagy and mitophagy markers, which would be associated with greater metabolic flexibility following a high-fat meal (HFM). MethodsMuscle biopsies were collected to determine differences in autophagy and mitophagy protein markers and metabolic flexibility under fasting conditions and 4 h following a HFM between endurance-trained male runners (n = 10) and sedentary, non-obese controls (n = 9). ResultsMaximal oxygen consumption (ml·kg·min−1) was approximately 50% higher (p < 0.05) in endurance-trained runners compared with sedentary controls (65.8 ± 2.3 and 43.1 ± 3.4, respectively). Autophagy markers were similar between groups. Mitophagy and mitochondrial dynamics protein markers were significantly higher in skeletal muscle of endurance-trained runners compared with sedentary controls in the fasted state, although unaffected by the HFM. Skeletal muscle metabolic flexibility was similar between groups when fasted (p > 0.05), but increased in response to the HFM in endurance-trained athletes only (p < 0.005). Key mitophagy markers, phospho-Pink1Thr257 and phospho-ParkinS65 (r = 0.64, p < 0.005), and phospo-ParkinSer65 and phospho-Drp1Ser616 (r = 0.70, p < 0.05) were correlated only within the endurance-trained group. Autophagy and mitophagy markers were not correlated with metabolic flexibility. ConclusionIn summary, mitophagy may be enhanced in endurance-trained runners based on elevated markers of mitophagy and mitochondrial dynamics. The HFM did not alter autophagy or mitophagy in either group. The absence of a relationship between mitophagy markers and metabolic flexibility suggests that mitophagy is not a key determinant of metabolic flexibility in a healthy population, but further investigation is warranted.

Intramuscular triglyceride synthesis: importance in muscle lipid partitioning in humans.

Intramuscular triglyceride (IMTG) concentration is elevated in insulin-resistant individuals and was once thought to promote insulin resistance. However, endurance-trained athletes have equivalent concentration of IMTG compared with individuals with type 2 diabetes, and have very low risk of diabetes, termed the "athlete's paradox." We now know that IMTG synthesis is positively related to insulin sensitivity, but the exact mechanisms for this are unclear. To understand the relationship between IMTG synthesis and insulin sensitivity, we measured IMTG synthesis in obese control subjects, endurance-trained athletes, and individuals with type 2 diabetes during rest, exercise, and recovery. IMTG synthesis rates were positively related to insulin sensitivity, cytosolic accumulation of DAG, and decreased accumulation of C18:0 ceramide and glucosylceramide. Greater rates of IMTG synthesis in athletes were not explained by alterations in FFA concentration, DGAT1 mRNA expression, or protein content. IMTG synthesis during exercise in Ob and T2D indicate utilization as a fuel despite unchanged content, whereas IMTG concentration decreased during exercise in athletes. mRNA expression for genes involved in lipid desaturation and IMTG synthesis were increased after exercise and recovery. Further, in a subset of individuals, exercise decreased cytosolic and membrane di-saturated DAG content, which may help explain insulin sensitization after acute exercise. These data suggest IMTG synthesis rates may influence insulin sensitivity by altering intracellular lipid localization, and decreasing specific ceramide species that promote insulin resistance.

The Right Heart: Acute and Chronic Issues.

Cardiovascular remodeling in response to sustained moderate and high-intensity exercise is a well-established phenomenon. Following more than a century of work focused on the left ventricle (LV), remodeling of the right side of the heart has recently become a topic of considerable scientific and clinical interest. Morphologic and functional changes have now been well documented in the right ventricle (RV) after isolated bouts of endurance exercise and in association with long-term sustained training. Although exercise-induced cardiac remodeling is classically viewed as an adaptive, clinically benign process, it has recently been hypothesized that repetitive bouts of intense exercise may trigger pathologic changes in the RV characterized by patchy fibrosis and a predisposition to arrhythmia. At present, this concept remains speculative due to the absence of definitive clinical data. While we await scientific clarification of this intriguing hypothesis, several practical clinical considerations are noteworthy. RV dilation is common among trained endurance athletes. As such, asymptomatic athletes with RV dilation do not require additional diagnostic evaluation unless dilation is accompanied by substantial decrements in systolic function or other structural abnormalities suggestive of genetic heart disease. In contrast, RV dilation among athletes with either symptoms or a family history of genetic heart disease requires extensive multi-modality assessment including maximal effort-limited exercise testing, ambulatory rhythm monitoring, advanced non-invasive imaging, and invasive electrophysiology study. This review will discuss the contemporary understanding of how the RV responds to exercise with an emphasis on the relevance of this phenomenon in clinical cardiovascular practice.

Evaluation of Muscle microRNA Expression in Relation to Human Peripheral Insulin Sensitivity: A Cross-Sectional Study in Metabolically Distinct Subject Groups.

In recent years, several microRNAs (miRNAs)—post-transcriptional regulators of gene expression—have been linked to the regulation of peripheral insulin sensitivity. Many of these studies, however, have been conducted in cell or animal models and the few human studies available lack adequate measurements of peripheral insulin sensitivity. In the present study, we examined the expression of 25 miRNAs, putatively involved in (peripheral) insulin sensitivity, in skeletal muscle biopsies from extensively phenotyped human individuals, widely ranging in insulin sensitivity. To identify miRNAs expressed in skeletal muscle and associated with insulin sensitivity and type 2 diabetes, a comprehensive PubMed-based literature search was performed. Subsequently, the expression of selected miRNAs was determined by RT-qPCR using predesigned 384-well Pick-&-Mix miRNA PCR Panel plates in muscle biopsies from type 2 diabetes patients, non-diabetic obese/overweight individuals, lean sedentary individuals and endurance-trained athletes. In all subjects, peripheral insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. The literature search resulted in 25 candidate miRNAs, 6 of which were differentially expressed in human type 2 diabetes compared to non-diabetic obese/overweight individuals. In turn, four of these miRNAs, i.e., miRNA27a-3p (r = −0.45, p = 0.0012), miRNA-29a-3p (r = −0.40, p = 0.0052), miRNA-29b-3p (r = −0.70, p < 0.0001) and miRNA-29c-3p (r = −0.50, p = 0.0004) demonstrated strong negative correlations with peripheral insulin sensitivity across all four subject groups. We identified miR-27a-3p and all members of the miRNA-29 family as potential regulatory players in insulin sensitivity in humans. These miRNA's may represent interesting novel targets for maintaining or improving insulin sensitivity.

Do nitric oxide synthase and cyclooxygenase contribute to sweating response during passive heating in endurance-trained athletes?

The aim of our study was to determine if habitual endurance training can influence the relative contribution of nitric oxide synthase (NOS) and cyclooxygenase (COX) in the regulation of sweating during a passive heat stress in young adults. Ten trained athletes and nine untrained counterparts were passively heated until oral temperature (as estimated by sublingual temperature, Tor) increased by 1.5°C above baseline resting. Forearm sweat rate (ventilated capsule) was measured at three skin sites continuously perfused with either lactated Ringer's solution (Control), 10 mmol/L NG‐nitro‐L‐arginine methyl ester (L‐NAME, non‐selective NOS inhibitor), or 10 mmol/L ketorolac (Ketorolac, non‐selective COX inhibitor) via intradermal microdialysis. Sweat rate was averaged for each 0.3°C increase in Tor. Sweat rate at the L‐NAME site was lower than Control following a 0.9 and 1.2°C increase in Tor in both groups (all P ≤ 0.05). Relative to the Control site, NOS‐inhibition reduced sweating similarly between the groups (P = 0.51). Sweat rate at the Ketorolac site was not different from the Control at any levels of Tor in both groups (P > 0.05). Nevertheless, a greater sweat rate was measured at the end of heating in the trained as compared to the untrained individuals (P ≤ 0.05). We show that NOS contributes similarly to sweating in both trained and untrained individuals during a passive heat stress. Further, no effect of COX on sweating was measured for either group. The greater sweat production observed in endurance‐trained athletes is likely mediated by factors other than NOS‐ and COX‐dependent mechanisms.

Post-exercise serum hepcidin levels were unaffected by hypoxic exposure during prolonged exercise sessions.

The purpose of the present study was to determine the influence of hypoxic exposure during prolonged endurance exercise sessions (79 min in total) on post-exercise hepcidin levels in trained male endurance athletes. Ten endurance athletes (mean ± standard deviation; height: 169.8 ± 7.1 cm, weight: 57.1 ± 5.0 kg) conducted two endurance exercise sessions under either a normobaric hypoxic condition [inspired O2 fraction (FiO2) = 14.5%] or a normoxic condition (FiO2 = 20.9%). Exercise consisted of 10 × 3 min running on a treadmill at 95% of maximal oxygen uptake () with 60s of active rest at 60% of . After 10 min of rest, they subsequently performed 30 min of continuous running at 85% of . Running velocities were significantly lower in the HYPO than in the NOR (P < 0.0001). Exercise-induced blood lactate elevation was significantly greater in the HYPO (P < 0.01). There were significant increases in plasma interleukin-6, serum iron, and blood glucose levels after exercise, with no significant difference between the trials [interaction (trial × time) or main effect for trial, P > 0.05]. Serum hepcidin levels increased significantly 120 min after exercise (HYPO: from 10.7 ± 9.4 ng/mL to 15.8 ± 11.2 ng/mL; NOR: from 7.9 ± 4.7 ng/mL to 13.2 ± 7.9 ng/mL, P < 0.05), and no difference was observed between the trials. In conclusion, endurance exercise at lower running velocity in hypoxic conditions resulted in similar post-exercise hepcidin elevations as higher running velocity in normoxic conditions.

Absence of resting cardiovascular dysfunction in middle-aged endurance-trained athletes with exaggerated exercise blood pressure responses.

Untrained individuals with exaggerated blood pressure (EBP) responses to graded exercise testing are characterized as having resting dysfunction of the sympathetic and cardiovascular systems. The purpose of this study was to determine the resting cardiovascular state of endurance-trained individuals with EBP through a comparison of normotensive athletes with and without EBP. EBP was defined as a maximal systolic blood pressure (SBP) at least 190 mmHg and at least 210 mmHg for women and men respectively, in response to a graded exercise test. Twenty-two life-long endurance-trained athletes (56 ± 5 years, 16 men) with EBP (EBP+) and 11 age and sex-matched athletes (55 ± 5 years, eight men) without EBP (EBP-) participated in the study. Sympathetic reactivity was assessed using BP responses to a cold pressor test, isometric handgrip exercise, and postexercise muscle ischemia. Resting left ventricular structure and function was assessed using two-dimensional echocardiography, whereas central arterial stiffness was assessed using carotid-to-femoral pulse wave velocity. Calf vascular conductance was measured at rest and peak postexercise using strain-gauge plethysmography. All sympathetic reactivity, left ventricular, and arterial stiffness indices were similar between groups. There was no between-group difference in resting vascular conductance, whereas peak vascular conductance was higher in EBP+ relative to EBP- (1.81 ± 0.65 vs. 1.45 ± 0.32 ml/100 ml/min/mmHg, P < 0.05). Findings from this study suggest that athletes with EBP do not display the resting cardiovascular state typically observed in untrained individuals with EBP. This response in athletes, therefore, is likely a compensatory mechanism to satisfy peripheral blood-flow demands rather than indicative of latent dysfunction.

Effects of Mental Fatigue on Endurance Performance in the Heat.

Mental fatigue is a psychobiological state caused by prolonged periods of demanding cognitive activity and has been observed to decrease time trial (TT) endurance performance by ∼3.5% in normal ambient temperatures. Recently, it has been suggested that heat may augment the negative effect of mental fatigue on cognitive performance, raising the question whether it may also amplify the effect of mental fatigue on TT performance. In 30°C and 30% relative humidity, 10 endurance-trained male athletes (mean ± SD; age = 22 ± 3 yr, Wmax = 332 ± 41 W) completed two experimental conditions: intervention (I; 45-min Stroop task) and control (C; 45-min documentary). Pre- and postintervention/control, cognitive performance was followed up with a 5-min Flanker task. Thereafter, subjects cycled for 45 min at a fixed pace equal to 60% Wmax, immediately followed by a self-paced TT in which they had to produce a fixed amount of work (equal to cycling 15 min at 80% Wmax) as fast as possible. Self-reported mental fatigue was significantly higher after I compared with C (P < 0.05). Moreover EEG measures also indicated the occurrence of mental fatigue during the Stroop (P < 0.05). TT did not differ between conditions (I = 906 ± 30 s, C = 916 ± 29 s). Throughout exercise, physiological (HR, blood lactate, core, and skin temperature) and perceptual measures (perception of effort and thermal sensation) were not affected by mental fatigue. No negative effects of mild mental fatigue were observed on performance and the physiological and perceptual responses to endurance exercise in the heat. Most plausibly, mild mental fatigue does not reduce endurance performance when the brain is already stressed by a hot environment.

Effects of macro- and micronutrients on exercise-induced hepcidin response in highly trained endurance athletes.

Iron deficiency has ergolytic effects on athletic performance. Exercise-induced inflammation impedes iron absorption in the digestive tract by upregulating the expression of the iron regulatory protein, hepcidin. Limited research indicates the potential of specific macro- and micronutrients on blunting exercise-induced hepcidin. Therefore, we investigated the effects of postexercise supplementation with protein and carbohydrate (CHO) and vitamins D3 and K2 on the postexercise hepcidin response. Ten highly trained male cyclists (age: 26.9 ± 6.4 years; maximal oxygen uptake: 67.4 ± 4.4 mL·kg-1·min-1 completed 4 cycling sessions in a randomized, placebo-controlled, single-blinded, triple-crossover study. Experimental days consisted of an 8-min warm-up at 50% power output at maximal oxygen uptake, followed by 8 × 3-min intervals at 85% power output at maximal oxygen uptake with 1.5 min at 60% power output at maximal oxygen uptake between each interval. Blood samples were collected pre- and postexercise, and at 3 h postexercise. Three different drinks consisting of CHO (75 g) and protein (25 g) with (VPRO) or without (PRO) vitamins D3 (5000 IU) and K2 (1000 μg), or a zero-calorie control drink (PLA) were consumed immediately after the postexercise blood sample. Results showed that the postexercise drinks had no significant (p ≥ 0.05) effect on any biomarker measured. There was a significant (p < 0.05) increase in hepcidin and interleukin-6 following intense cycling intervals in the participants. Hepcidin increased significantly (p < 0.05) from baseline (nmol·L-1: 9.94 ± 8.93, 14.18 ± 14.90, 10.44 ± 14.62) to 3 h postexercise (nmol·L-1: 22.27 ± 13.41, 25.44 ± 11.91, 22.57 ± 15.57) in VPRO, PRO, and PLA, respectively. Contrary to our hypothesis, the drink compositions used did not blunt the postexercise hepcidin response in highly trained athletes.

Endurance training selectively increases high-density lipoprotein-bound sphingosine-1-phosphate in the plasma.

Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid that is found in relatively high concentration in human plasma. Erythrocytes, endothelial cells, and activated platelets are the main sources of circulating S1P. The majority of plasma S1P is transported bound to high-density lipoprotein (HDL) and albumin. In recent years, HDL-bound S1P attracted much attention due to its cardioprotective and anti-atherogenic properties. We have previously found that endurance-trained athletes are characterized by higher plasma S1P concentration compared to untrained individuals. This finding prompted us to examine the effect of endurance training on S1P metabolism in blood. Thirteen healthy, untrained, male subjects completed an 8-week training program on a rowing ergometer. Three days before the first, and 3days after the last training session, blood samples were drawn from an antecubitalvein. We found that total plasma S1P concentration was increased after the training. Further analysis of different plasma fractions showed that the training selectively elevated HDL-bound S1P. This effect was associated with activation of sphingosine kinase in erythrocytes and platelets and enhanced S1P release from red blood cells. We postulate that increase in HDL-bound S1P level is one of the mechanisms underlying beneficial effects of regular physical activity on cardiovascular diseases.

Changes in the plasma levels of myokines after different physical exercises in athletes and untrained individuals

The influence of dynamic and static load on the plasma level of myokines in strength-and endurance-trained athletes and untrained subjects has been studied. The range of myokines has been found to depend on the type of loads and the level of fitness. Dynamic and static exercises have different effects on the level of myokines in athletes and untrained subjects. The dynamic load increases the level of IL-6 and IL-8 in the plasma of athletes, while the static load increases the concentration of IL-15 and LIF. At the same time, no increase in the level of IL-8 after cyclic loading or in IL-15 after a static load has been observed in the control group. These differences may be based on a number of mechanisms. The cellular composition of skeletal muscles and the phenotypic features of muscle fibers, changing as a result of regular exercise, can modify the processes of myokine production. However, the processes of transcription in muscle fibers are much more important; the most important ones are HIF-1α, [Ca2+]i and [Na+]i/[K+]i-dependent intracellular signaling pathways. The modification of these mechanisms caused by different physical loads and intensity is of great interest since it is a promising way to influence the metabolic processes at the cellular and systemic levels, which is very helpful in both improving athletic performance and correcting metabolic disorders in a number of socially significant diseases.

Dynamic and Static Exercises Differentially Affect Plasma Cytokine Content in Elite Endurance- and Strength-Trained Athletes and Untrained Volunteers.

Extensive exercise increases the plasma content of IL-6, IL-8, IL-15, leukemia inhibitory factor (LIF), and several other cytokines via their augmented transcription in skeletal muscle cells. However, the relative impact of aerobic and resistant training interventions on cytokine production remains poorly defined. In this study, we compared effects of dynamic and static load on cytokine plasma content in elite strength- and endurance-trained athletes vs. healthy untrained volunteers. The plasma cytokine content was measured before, immediately after, and 30 min post-exercise using enzyme-linked immunosorbent assay. Pedaling on a bicycle ergometer increased IL-6 and IL-8 content in the plasma of trained athletes by about 4- and 2-fold, respectively. In contrast to dynamic load, weightlifting had negligible impact on these parameters in strength exercise-trained athletes. Unlike IL-6 and IL-8, dynamic exercise had no impact on IL-15 and LIF, whereas static load increases the content of these cytokines by ~50%. Two-fold increment of IL-8 content seen in athletes subjected to dynamic exercise was absent in untrained individuals, whereas the ~50% increase in IL-15 triggered by static load in the plasma of weightlifting athletes was not registered in the control group. Thus, our results show the distinct impact of static and dynamic exercises on cytokine content in the plasma of trained athletes. They also demonstrate that both types of exercises differentially affect cytokine content in plasma of athletes and untrained persons.

The effect of time-of-day of training during Ramadan on physiological parameters in highly trained endurance athletes

We investigated the effect of Ramadan fasting on maximal aerobic velocity (MAV), time to exhaustion (tlim100), performance in running 3000-m in runners who trained at 09:00, 14:00, and 22:00 h. Twenty-four middle- and long-distance runners (28.5 ± 10.6 years) were assigned to 3 groups of 8 participants: an afternoon group (AG) (who trained between 14:00 and 16:00 h), a morning group (MG) (who trained between 09:00 and 11:00 h), and an evening group (EG) (who trained between 22:00 and 24:00 h). Before, at mid-, and after Ramadan, MAV and maximal oxygen uptake () were significantly higher (p < 0.01) in the AG and MG groups compared to the EG group. Before and after Ramadan, the times recorded for the 3000-m running exercise were significantly higher (p < 0.01) and tlim100 was significantly lower (p < 0.001) in the EG and MG groups compared to the AG groups. In conclusion, afternoon training during Ramadan might be more effective than morning or evening training for the enhancement of aerobic capacity.

Branched-chain amino acids administration suppresses endurance exercise-related activation of ubiquitin proteasome signaling in trained human skeletal muscle.

We tested whether post exercise ingestion of branched-chain amino acids (BCAA<10g) is sufficient to activate signaling associated with muscle protein synthesis and suppress exercise-induced activation of mechanisms associated with proteolysis in endurance-trained human skeletal muscle. Nine endurance-trained athletes performed a cycling bout with and without BCAA ingestion (0.1g/kg). Post exercise ACCSer79/222 phosphorylation (endogenous marker of AMPK activity) was increased (~3-fold, P<0.05) in both sessions. No changes were observed in IGF1 mRNA isoform expression or phosphorylation of the key anabolic markers - p70S6K1Thr389 and eEF2Thr56 - between the sessions. BCAA administration suppressed exercise-induced expression of mTORC1 inhibitor DDIT4 mRNA, eliminated activation of the ubiquitin proteasome system, detected in the control session as decreased FOXO1Ser256 phosphorylation (0.83-fold change, P<0.05) and increased TRIM63 (MURF1) expression (2.4-fold, P<0.05). Therefore, in endurance-trained human skeletal muscle, post exercise BCAA ingestion partially suppresses exercise-induced expression of PGC-1a mRNA, activation of ubiquitin proteasome signaling, and suppresses DDIT4 mRNA expression.

The impact of mental fatigue on a preloaded cycling-time trial in the heat

Introduction: Mental fatigue is a change in psychobiological state caused by prolonged periods of demanding cognitive activity and has been observed to decrease whole-body endurance performance [1-5]. Recently a decreased resting-state cerebral blood-flow in the fronto-parietal cortex in the heat compared to in thermoneutral temperature was observed [6], raising the question whether mental fatigue may be even more detrimental for wholebody endurance performance in the heat. In normal ambient temperatures, performancedecrements of 5% [2] and 2% [4] have been observed in self-paced time trials (TT) due to mental fatigue.  Aim: To examine the effect of mental fatigue on a subsequent whole-body endurance performance and brain activity in the heat.  Methods: In 30°C and 30% relative humidity, ten endurance-trained male athletes (Age: 22 ± 3y; W max : 332 ± 41W; PL 3 [7]) completed two experimental trials in a single blind, randomized, cross-over design. A 5min Flanker was completed preceding and immediately following a 45min Stroop task [mental fatigue (MF)] or watching a documentary [control (C)]. Thereafter subjects cycled for 45min at a fixed pace equal to 60% Wmax, immediately followed by a self-paced TT in which they had to produce a fixed amount of energy (equal to cycling 15min at 80% W max ) as fast as possible. In the TT subjects started at 80% of their Wmax and were free to in- or decrease the resistance as desired from outset. Electroencephalographic measures (32 electrodes) were recorded continuously during the cognitive tasks. Power output, heart rate, blood lactate, core and skin temperature, thermal sensation, ratings of perceived exertion, NASA-TLX and mental fatigue-VAS-scale (M-VAS) were assessed throughout the protocol.  Results: Electroencephalographic (P3b-amplitude decreased and I±1-activity increased (p<0,05; fig. 1)) and perceptual (M-VAS increased (p<0,05)) measures were significantly altered in the Stroop compared to during the documentary. M-VAS was also significantly increased in the first 15min of the fixed intensity part of the physical performance. The induced mental fatigue did however not influence any physiological (heart rate, blood lactate, core or skin temperature) or perceptual (ratings of perceived exertion and thermal sensation) measure during the fixed intensity part. TT-time also did not differ between conditions (MF: 906 ± 30s, C: 916 ± 29s; Fig. 2). Individually three participants performed worse when mentally fatigued, four better and three replicated the same TT-time within a 5s-marge in both conditions (Fig. 2).  Conclusion: Although a mild mental fatigue was induced in the heat, no negative effect was observed on physiological, perceptual or behavioral measures during the fixed intensity part or the TT. There are three possible explanations for these results. Firstly, the mild mental fatigue was insufficient to alter endurance performance and/or endurance trained athletes are resistant to the negative effects of mental exertion on subsequent endurance performance [8]. Another plausible explanation is that mild mental fatigue does not reduce endurance performance when the brain is already stressed by a hot environment when the brain is already stressed by a hot environment.

Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle.

In human skeletal muscles, the current view is that the capacity for mitochondrial energy production, and thus endurance capacity, is set by the mitochondria volume. However, increasing the mitochondrial inner membrane surface comprises an alternative mechanism for increasing the energy production capacity. In the present study, we show that mitochondrial inner membranes in leg muscles of endurance-trained athletes have an increased ratio of surface per mitochondrial volume. We show a positive correlation between this ratio and whole body oxygen uptake and muscle fibre mitochondrial content. The results obtained in the present study help us to understand modulation of mitochondrial function, as well as how mitochondria can increase their oxidative capacity with increased demand. Mitochondrial energy production involves the movement of protons down a large electrochemical gradient via ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in mitochondria is assumed to be constant. However, recent experimental studies have shown that respiration per mitochondria varies. Modelling studies have hypothesized that this variation in respiration per mitochondria depends on plasticity in cristae density, although current evidence for such a mechanism is lacking. In the present study, we confirm this hypothesis by showing that, in human skeletal muscle, and in contrast to the current view, the mitochondrial cristae density is not constant but, instead, exhibits plasticity with long-term endurance training. Furthermore, we show that frequently recruited mitochondria-enriched fibres have significantly increased cristae density and that, at the whole-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish an elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose that this mechanism allows evasion of the trade-off between cell occupancy by mitochondria and other cellular constituents, as well as improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements.