Energetic responses of head-out water immersion at different temperatures during post-exercise recovery and its consequence on anaerobic mechanical power.

PURPOSE: While exercise recovery may be beneficial from a physiological point of view, it may be detrimental to subsequent anaerobic performance. To investigate the energetic responses of water immersion at different temperatures during post-exercise recovery and its consequences on subsequent anaerobic performance, a randomized and controlled crossover experimental design was performed with 21 trained cyclists. METHOD: Participants were assigned to receive three passive recovery strategies during 10 min after a Wingate Anaerobic Test (WAnT): control (CON: non-immersed condition), cold water immersion (CWI: 20 â„ƒ), and hot water immersion (HWI: 40 â„ƒ). Blood lactate, cardiorespiratory, and mechanical outcomes were measured during the WAnT and its recovery. Time constant (τ), asymptotic value, and area under the curve (AUC) were quantified for each physiologic parameter during recovery. After that, a second WAnT test and 10-min recovery were realized in the same session. RESULTS: Regardless the water immersion temperature, water immersion increased [Formula: see text] (+ 18%), asymptote ([Formula: see text]+ 16%, [Formula: see text] + 13%, [Formula: see text] + 17%, HR + 16%) and AUC ([Formula: see text]+ 27%, [Formula: see text] + 18%, [Formula: see text] + 20%, HR + 25%), while decreased [Formula: see text] (- 33%). There was no influence of water immersion on blood lactate parameters. HWI improved the mean power output during the second WAnT (2.2%), while the CWI decreased 2.4% (P < 0.01). CONCLUSION: Independent of temperature, water immersion enhanced aerobic energy recovery without modifying blood lactate recovery. However, subsequent anaerobic performance was increased only during HWI and decreased during CWI. Despite higher than in other studies, 20 °C effectively triggered physiological and performance responses. Water immersion-induced physiological changes did not predict subsequent anaerobic performance.

Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier Integrity.

RATIONALE: Endothelial cells (ECs) are highly glycolytic and generate the majority of their energy via the breakdown of glucose to lactate. At the same time, a main role of ECs is to allow the transport of glucose to the surrounding tissues. GLUT1 (glucose transporter isoform 1/Slc2a1) is highly expressed in ECs of the central nervous system (CNS) and is often implicated in blood-brain barrier (BBB) dysfunction, but whether and how GLUT1 controls EC metabolism and function is poorly understood. OBJECTIVE: We evaluated the role of GLUT1 in endothelial metabolism and function during postnatal CNS development as well as at the adult BBB. METHODS AND RESULTS: Inhibition of GLUT1 decreases EC glucose uptake and glycolysis, leading to energy depletion and the activation of the cellular energy sensor AMPK (AMP-activated protein kinase), and decreases EC proliferation without affecting migration. Deletion of GLUT1 from the developing postnatal retinal endothelium reduces retinal EC proliferation and lowers vascular outgrowth, without affecting the number of tip cells. In contrast, in the brain, we observed a lower number of tip cells in addition to reduced brain EC proliferation, indicating that within the CNS, organotypic differences in EC metabolism exist. Interestingly, when ECs become quiescent, endothelial glycolysis is repressed, and GLUT1 expression increases in a Notch-dependent fashion. GLUT1 deletion from quiescent adult ECs leads to severe seizures, accompanied by neuronal loss and CNS inflammation. Strikingly, this does not coincide with BBB leakiness, altered expression of genes crucial for BBB barrier functioning nor reduced vascular function. Instead, we found a selective activation of inflammatory and extracellular matrix related gene sets. CONCLUSIONS: GLUT1 is the main glucose transporter in ECs and becomes uncoupled from glycolysis during quiescence in a Notch-dependent manner. It is crucial for developmental CNS angiogenesis and adult CNS homeostasis but does not affect BBB barrier function.

Rating of perceived exertion in maximal incremental tests during head-out water-based aerobic exercises.

The present study aimed to assess the relationship between rating of perceived exertion (RPE) and percentage of peak oxygen uptake ([Formula: see text]) during three head-out water-based aerobic exercises. In addition, the RPE at the second ventilatory threshold (VT2) was also compared among them. Twenty young women performed head-out water-based maximal tests for the exercises stationary running (SR), frontal kick (FK) and cross-country skiing (CCS). RPE was monitored during the tests and the values corresponding to VT2 and training zones corresponding to 50-59%, 60-69%, 70-79%, 80-89% and [Formula: see text] were determined. Regression analysis, descriptive statistics and ANOVA with repeated measures were used. Significant relationships were observed between the RPE and [Formula: see text] (r = 0.858-0.893; P < 0.001) for all head-out water-based aerobic exercises. Average RPE ranged from 12.1-12.7 in the training zone corresponding to 50-59%, from 13.7-14.8 to 60-69%, from 15.8-16.4 to 70-79%, from 17.3-18.1 to 80-89% and from 18.5-18.9 to [Formula: see text]. No significant differences were found among the three head-out water-based aerobic exercises at VT2 (P > 0.05; SR: 16.1 ± 0.9, FK: 16.7 ± 1.5, CCS: 15.9 ± 1.3). The results support the use of RPE to control the relative intensity of training during head-out water-based aerobic exercises and indicate values near to 16-17 when targeting VT2 intensity for young women.

MME+ fibro-adipogenic progenitors are the dominant adipogenic population during fatty infiltration in human skeletal muscle.

Fatty infiltration, the ectopic deposition of adipose tissue within skeletal muscle, is mediated via the adipogenic differentiation of fibro-adipogenic progenitors (FAPs). We used single-nuclei and single-cell RNA sequencing to characterize FAP heterogeneity in patients with fatty infiltration. We identified an MME+ FAP subpopulation which, based on ex vivo characterization as well as transplantation experiments, exhibits high adipogenic potential. MME+ FAPs are characterized by low activity of WNT, known to control adipogenic commitment, and are refractory to the inhibitory role of WNT activators. Using preclinical models for muscle damage versus fatty infiltration, we show that many MME+ FAPs undergo apoptosis during muscle regeneration and differentiate into adipocytes under pathological conditions, leading to a reduction in their abundance. Finally, we utilized the varying fat infiltration levels in human hip muscles and found less MME+ FAPs in fatty infiltrated human muscle. Altogether, we have identified the dominant adipogenic FAP subpopulation in skeletal muscle.

Exercise-induced angiogenesis is dependent on metabolically primed ATF3/4+ endothelial cells.

Exercise is a powerful driver of physiological angiogenesis during adulthood, but the mechanisms of exercise-induced vascular expansion are poorly understood. We explored endothelial heterogeneity in skeletal muscle and identified two capillary muscle endothelial cell (mEC) populations that are characterized by differential expression of ATF3/4. Spatial mapping showed that ATF3/4+ mECs are enriched in red oxidative muscle areas while ATF3/4low ECs lie adjacent to white glycolytic fibers. In vitro and in vivo experiments revealed that red ATF3/4+ mECs are more angiogenic when compared with white ATF3/4low mECs. Mechanistically, ATF3/4 in mECs control genes involved in amino acid uptake and metabolism and metabolically prime red (ATF3/4+) mECs for angiogenesis. As a consequence, supplementation of non-essential amino acids and overexpression of ATF4 increased proliferation of white mECs. Finally, deleting Atf4 in ECs impaired exercise-induced angiogenesis. Our findings illustrate that spatial metabolic angiodiversity determines the angiogenic potential of muscle ECs.

The effect of resistance training, detraining and retraining on muscle strength and power, myofibre size, satellite cells and myonuclei in older men.

INTRODUCTION: Ageing is associated with an attenuated hypertrophic response to resistance training and periods of training interruptions. Hence, elderly would benefit from the 'muscle memory' effects of resistance training on muscle strength and mass during detraining and retraining. As the underlying mechanisms are not yet clear, this study investigated the role of myonuclei during training, detraining and retraining by using PCM1 labelling in muscle cross-sections of six older men. METHODS: Knee extension strength and power were measured in 30 older men and 10 controls before and after 12 weeks resistance training and after detraining and retraining of similar length. In a subset, muscle biopsies from the vastus lateralis were taken for analysis of fibre size, fibre type distribution, Pax7+ satellite cell number and myonuclear domain size. RESULTS: Resistance training increased knee extension strength and power parameters (+10 to +36%, p < .001) and decreased the frequency of type IIax fibres by half (from 20 to 10%, p = .034). Detraining resulted in a modest loss of strength and power (-5 to -15%, p ≤ .004) and a trend towards a fibre-type specific decrease in type II fibre cross-sectional area (-17%, p = .087), type II satellite cell number (-30%, p = .054) and type II myonuclear number (-12%, p = .084). Less than eight weeks of retraining were needed to reach the post-training level of one-repetition maximum strength. Twelve weeks of retraining were associated with type II fibre hypertrophy (+29%, p = .050), which also promoted an increase in the number of satellite cells (+72%, p = .036) and myonuclei (+13%, p = .048) in type II fibres. Changes in the type II fibre cross-sectional area were positively correlated with changes in the myonuclear number (Pearson's r between 0.40 and 0.73), resulting in a stable myonuclear domain. CONCLUSION: Gained strength and power and fibre type changes were partially preserved following 12 weeks of detraining, allowing for a fast recovery of the 1RM performance following retraining. Myonuclear number tended to follow individual changes in type II fibre size, which is in support of the myonuclear domain theory.

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner.

BACKGROUND: Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. Exercise stimulates SC accumulation and myonuclear accretion. To what extent exercise training at different mechanical loads drive SC contribution to myonuclei however is unknown. RESULTS: By performing SC fate tracing experiments, we show that 8 weeks of voluntary wheel running increased SC contribution to myofibers in mouse plantar flexor muscles in a load-dependent, but fiber type-independent manner. Increased SC fusion however was not exclusively linked to muscle hypertrophy as wheel running without external load substantially increased SC fusion in the absence of fiber hypertrophy. Due to nuclear propagation, nuclear fluorescent fate tracing mouse models were inadequate to quantify SC contribution to myonuclei. Ultimately, by performing fate tracing at the DNA level, we show that SC contribution mirrors myonuclear accretion during exercise. CONCLUSIONS: Collectively, mechanical load during exercise independently promotes SC contribution to existing myofibers. Also, due to propagation of nuclear fluorescent reporter proteins, our data warrant caution for the use of existing reporter mouse models for the quantitative evaluation of satellite cell contribution to myonuclei.

Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization.

Endothelial cell (EC)-derived signals contribute to organ regeneration, but angiocrine metabolic communication is not described. We found that EC-specific loss of the glycolytic regulator pfkfb3 reduced ischemic hindlimb revascularization and impaired muscle regeneration. This was caused by the reduced ability of macrophages to adopt a proangiogenic and proregenerative M2-like phenotype. Mechanistically, loss of pfkfb3 reduced lactate secretion by ECs and lowered lactate levels in the ischemic muscle. Addition of lactate to pfkfb3-deficient ECs restored M2-like polarization in an MCT1-dependent fashion. Lactate shuttling by ECs enabled macrophages to promote proliferation and fusion of muscle progenitors. Moreover, VEGF production by lactate-polarized macrophages was increased, resulting in a positive feedback loop that further stimulated angiogenesis. Finally, increasing lactate levels during ischemia rescued macrophage polarization and improved muscle reperfusion and regeneration, whereas macrophage-specific mct1 deletion prevented M2-like polarization. In summary, ECs exploit glycolysis for angiocrine lactate shuttling to steer muscle regeneration from ischemia.

Metabolic regulation of exercise-induced angiogenesis.

Skeletal muscle relies on an ingenious network of blood vessels, which ensures optimal oxygen and nutrient supply. An increase in muscle vascularization is an early adaptive event to exercise training, but the cellular and molecular mechanisms underlying exercise-induced blood vessel formation are not completely clear. In this review, we provide a concise overview on how exercise-induced alterations in muscle metabolism can evoke metabolic changes in endothelial cells (ECs) that drive muscle angiogenesis. In skeletal muscle, angiogenesis can occur via sprouting and splitting angiogenesis and is dependent on vascular endothelial growth factor (VEGF) signaling. In the resting muscle, VEGF levels are controlled by the estrogen-related receptor γ (ERRγ). Upon exercise, the transcriptional coactivator peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC1α) orchestrates several adaptations to endurance exercise within muscle fibers and simultaneously promotes transcriptional activation of Vegf expression and increased muscle capillary density. While ECs are highly glycolytic and change their metabolism during sprouting angiogenesis in development and disease, a similar role for EC metabolism in exercise-induced angiogenesis in skeletal muscle remains to be elucidated. Nonetheless, recent studies have illustrated the importance of endothelial hydrogen sulfide and sirtuin 1 (SIRT1) activity for exercise-induced angiogenesis, suggesting that EC metabolic reprogramming may be fundamental in this process. We hypothesize that the exercise-induced angiogenic response can also be modulated by metabolic crosstalk between muscle and the endothelium. Defining the underlying molecular mechanisms responsible for skeletal muscle angiogenesis in response to exercise will yield valuable insight into metabolic regulation as well as the determinants of exercise performance.

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control.

BACKGROUND: Intramuscular fatty infiltration is generally associated with the accumulation of white adipocytes in skeletal muscle and unfavourable metabolic outcomes. It is, however, still unclear whether intramuscular adipocytes could also acquire a brown-like phenotype. Here, we detected intramuscular expression of brown adipocyte markers during fatty infiltration in an obesity-resistant mouse strain and extensively compared the potential of two different stem cell populations residing in skeletal muscle to differentiate into brown-like adipocytes. METHODS: Fatty infiltration was induced using intramuscular glycerol or cardiotoxin injection in the tibialis anterior muscles of young or aged 129S6/SvEvTac (Sv/129) mice or interleukin-6 (IL-6) knockout mice, and the expression of general and brown adipocyte markers was assessed after 4 weeks. Fibro/adipogenic progenitors (FAPs) and myogenic progenitors were prospectively isolated using fluorescence-activated cell sorting from skeletal muscle of male and female C57Bl6/6J and Sv/129 mice, and monoclonal and polyclonal cultures were treated with brown adipogenic medium. Additionally, FAPs were differentiated with medium supplemented or not with triiodothyronine. RESULTS: Although skeletal muscle expression of uncoupling protein 1 (Ucp1) was barely detectable in uninjected tibialis anterior muscle, it was drastically induced following intramuscular adipogenesis in Sv/129 mice and further increased in response to beta 3-adrenergic stimulation. Intramuscular Ucp1 expression did not depend on IL-6 and was preserved in aged skeletal muscle. Myogenic progenitors did not form adipocytes neither in polyclonal nor monoclonal cultures. Fibro/adipogenic progenitors, on the other hand, readily differentiated into brown-like, UCP1+ adipocytes. Uncoupling protein 1 expression in differentiated FAPs was regulated by genetic background, sex, and triiodothyronine treatment independently of adipogenic differentiation levels. CONCLUSIONS: Intramuscular adipogenesis is associated with increased Ucp1 expression in skeletal muscle from obesity-resistant mice. Fibro/adipogenic progenitors provide a likely source for intramuscular adipocytes expressing UCP1 under control of both genetic and hormonal factors. Therefore, FAPs constitute a possible target for therapies aiming at the browning of intramuscular adipose tissue and the metabolic improvement of skeletal muscle affected by fatty infiltration.

Relative Age Effect in Young Swiss Alpine Skiers From 2004 to 2011.

PURPOSE: To verify whether relative age effects (RAEs) occur among young male and female Swiss Alpine skiers of different age groups and performance levels. In addition, the efficacy of normalizing performance in physical tests to height and body mass to attenuate RAEs eventually present was tested. METHODS: The Swiss Ski Power Test consists of anthropometric measures and physical tests for coordination and speed, endurance, and strength and has been used since 2004 to evaluate 11- to 19-y-old Swiss competitive Alpine skiers. The authors analyzed the distribution of 6996 tests performed by 1438 male and 1031 female Alpine skiers between 2004 and 2011 according to the athletes' respective relative age quartiles. Differences in anthropometric measures and performance in physical tests according to quartile were assessed, and the possibility of attenuating eventual RAEs on performance by normalization of results to height and body mass was tested. RESULTS: RAEs were found among all female and male age groups, with no differences between age groups. While performance level did not affect RAE for male skiers, it influenced RAE among female skiers. RAEs also influenced results in all physical tests except upper-limb strength. Normalization of results to body mass attenuated most RAEs identified. CONCLUSION: Small RAEs are present among young Swiss competitive Alpine skiers and should be taken into account in training and selection settings to prevent the waste of possible future talents. When ranking junior athletes according to their performance in physical tests, normalization of results to body mass decreases the bias caused by RAEs.

An anthropometric and physical profile of young Swiss alpine skiers between 2004 and 2011.

PURPOSE: To describe the development of anthropometric and physical characteristics of young Swiss alpine skiers between 2004 and 2011, to compare them between age and performance-level groups, and to identify age- and sex-dependent reference values for the tests performed. METHODS: The Swiss-Ski Power Test includes anthropometric measures and physical tests for coordination and speed, strength, anaerobic capacity, and endurance. The authors analyzed the results of 8176 tests performed by 1579 male and 1109 female alpine skiers between 2004 and 2011. Subjects ranged between regional and national level of performance and were grouped according to their competition age groups (U12, 11 y; U14, 12-13 y; U16, 14-15 y; U18, 16-17 y; U21, 18-20 y) and performance level. RESULTS: A progressive increase in anthropometric measures and improvements in tests results with increasing age were found. For all tests, male athletes had better results than female athletes. Minor differences were observed in anthropometric characteristics between 2004 and 2011 (mostly <5%), while results of physical and coordinative tests showed significant improvements (up to more than 50% enhancement) or stability over the years. Differences between higher- and lower-level athletes were more pronounced in tests for lower-limb strength and anaerobic capacity. CONCLUSIONS: The presented profile of young Swiss alpine skiers highlights the improvements in different physical aspects along the maturation process and chronologically over a period of 7 y. Furthermore, reference values are provided for comparisons with alpine skiers or athletes from other sports.