Unlocking liver health: Can tackling myosteatosis spark remission in metabolic dysfunction-associated steatotic liver disease?

Myosteatosis is highly prevalent in metabolic dysfunction-associated steatotic liver disease (MASLD) and could reciprocally impact liver function. Decreasing muscle fat could be indirectly hepatoprotective in MASLD. We conducted a review to identify interventions reducing myosteatosis and their impact on liver function. Non-pharmacological interventions included diet (caloric restriction or lipid enrichment), bariatric surgery and physical activity. Caloric restriction in humans achieving a mean weight loss of 3% only reduces muscle fat. Lipid-enriched diet increases liver fat in human with no impact on muscle fat, except sphingomyelin-enriched diet which reduces both lipid contents exclusively in pre-clinical studies. Bariatric surgery, hybrid training (resistance exercise and electric stimulation) or whole-body vibration in human decrease both liver and muscle fat. Physical activity impacts both phenotypes by reducing local and systemic inflammation, enhancing insulin sensitivity and modulating the expression of key mediators of the muscle-liver-adipose tissue axis. The combination of diet and physical activity acts synergistically in liver, muscle and white adipose tissue, and further decrease muscle and liver fat. Several pharmacological interventions (patchouli alcohol, KBP-089, 2,4-dinitrophenol methyl ether, adipoRon and atglistatin) and food supplementation (vitamin D or resveratrol) improve liver and muscle phenotypes in pre-clinical studies by increasing fatty acid oxidation and anti-inflammatory properties. These interventions are effective in reducing myosteatosis in MASLD while addressing the liver disease itself. This review supports that disturbances in inter-organ crosstalk are key pathophysiological mechanisms involved in MASLD and myosteatosis pathogenesis. Focusing on the skeletal muscle might offer new therapeutic strategies to treat MASLD by modulating the interactions between liver and muscles.

Effects of plasmapheresis frequency on health status and exercise performance in men: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Most research studies on the effects of repeated plasma donation are observational with different study limitations, resulting in high uncertainty on the link between repeated plasma donation and health consequences. Here, we prospectively investigated the safety of intensive or less intensive plasma donation protocols. MATERIALS AND METHODS: Sixty-three male subjects participated in this randomized controlled trial and were divided into low-frequency (LF, once/month, n = 16), high-frequency (HF, three times/month, n = 16), very high-frequency (VHF, two times/week, n = 16) and a placebo (P, once/month, n = 15) groups. Biochemical, haematological, clinical, physiological and exercise-related data were collected before (D0), after 1½ months (D42) and after 3 months (D84) of donation. RESULTS: In VHF, red blood cells, haemoglobin and haematocrit levels decreased while reticulocyte levels increased from D0 to D84. In both HF and VHF, plasma ferritin levels were lower at D42 and D84 compared to D0. In VHF, plasma levels of albumin, immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) dropped from D0 to D42 and remained lower at D84 than at D0. In HF, plasma IgG, IgA and IgM were lower at D42, and IgG and IgM were lower at D84, compared to D0. Few adverse events were reported in HF and VHF. Repeated plasma donation had no effect on blood pressure, body composition or exercise performance. CONCLUSION: VHF plasmapheresis may result in a large reduction in ferritin and IgG levels. HF and VHF plasmapheresis may result in little to no difference in other biochemical, haematological, clinical, physiological and exercise-related parameters.

Fluid shear stress-induced mechanotransduction in myoblasts: Does it depend on the glycocalyx?

Muscle stem cells (MuSCs) are involved in muscle maintenance and regeneration. Mechanically loaded MuSCs within their native niche undergo tensile and shear deformations, but how MuSCs sense mechanical stimuli and translate these into biochemical signals regulating function and fate is still poorly understood. We aimed to investigate whether the glycocalyx is involved in the MuSC mechanoresponse, and whether MuSC morphology affects mechanical loading-induced pressure, shear stress, and fluid velocity distribution. FSS-induced deformation of active proliferating MuSCs (myoblasts) with intact or degraded glycocalyx was assessed by live-cell imaging. Glycocalyx-degradation did not significantly affect nitric oxide production, but reduced FSS-induced myoblast deformation and modulated gene expression. Finite-element analysis revealed that the distribution of FSS-induced pressure, shear stress, and fluid velocity on myoblasts was non-uniform, and the magnitude depended on myoblast morphology and apex-height. In conclusion, our results suggest that the glycocalyx does not play a role in NO production in myoblasts but might impact mechanotransduction and gene expression, which needs further investigation. Future studies will unravel the underlying mechanism by which the glycocalyx affects FSS-induced myoblast deformation, which might be related to increased drag forces. Moreover, MuSCs with varying apex-height experience different levels of FSS-induced pressure, shear stress, and fluid velocity, suggesting differential responsiveness to fluid shear forces.

Effects of an acute exercise bout in hypoxia on extracellular vesicle release in healthy and prediabetic subjects.

The purpose of this study is to investigate exosome-like vesicle (ELV) plasma concentrations and markers of multivesicular body (MVB) biogenesis in skeletal muscle in response to acute exercise. Seventeen healthy [body mass index (BMI): 23.5 ± 0.5 kg·m-2] and 15 prediabetic (BMI: 27.3 ± 1.2 kg·m-2) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia ([Formula: see text] 14.0%). Venous blood samples were taken before (T0), during (T30), and after (T60) exercise, and biopsies from m. vastus lateralis were collected before and after exercise. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards, followed by expression analyses of canonical ELV markers in skeletal muscle. In the healthy normoxic group, the total number of particles in the plasma increased during exercise from T0 to T30 (+313%) followed by a decrease from T30 to T60 (-53%). In the same group, an increase in TSG101, CD81, and HSP60 protein expression was measured after exercise in plasma ELVs; however, in the prediabetic group, the total number of particles in the plasma was not affected by exercise. The mRNA content of TSG101, ALIX, and CD9 was upregulated in skeletal muscle after exercise in normoxia, whereas CD9 and CD81 were downregulated in hypoxia. ELV plasma abundance increased in response to acute aerobic exercise in healthy subjects in normoxia, but not in prediabetic subjects, nor in hypoxia. Skeletal muscle analyses suggested that this tissue did not likely play a major role of the exercise-induced increase in circulating ELVs.

Higher strength gain after hypoxic vs normoxic resistance training despite no changes in muscle thickness and fractional protein synthetic rate.

Acute hypoxia has previously been suggested to potentiate resistance training-induced hypertrophy by activating satellite cell-dependent myogenesis rather than an improvement in protein balance in human. Here, we tested this hypothesis after a 4-week hypoxic vs normoxic resistance training protocol. For that purpose, 19 physically active male subjects were recruited to perform 6 sets of 10 repetitions of a one-leg knee extension exercise at 80% 1-RM 3 times/week for 4 weeks in normoxia (FiO2 : 0.21; n = 9) or in hypoxia (FiO2 : 0.135, n = 10). Blood and skeletal muscle samples were taken before and after the training period. Muscle fractional protein synthetic rate was measured over the whole period by deuterium incorporation into the protein pool and muscle thickness by ultrasound. At the end of the training protocol, the strength gain was higher in the hypoxic vs the normoxic group despite no changes in muscle thickness and in the fractional protein synthetic rate. Only early myogenesis, as assessed by higher MyoD and Myf5 mRNA levels, appeared to be enhanced by hypoxia compared to normoxia. No effects were found on myosin heavy chain expression, markers of oxidative metabolism and lactate transport in the skeletal muscle. Though the present study failed to unravel clearly the mechanisms by which hypoxic resistance training is particularly potent to increase muscle strength, it is important message to keep in mind that this training strategy could be effective for all athletes looking at developing and optimizing their maximal muscle strength.

Effect of hypoxic exercise on glucose tolerance in healthy and prediabetic adults.

This study aimed to investigate the mechanisms known to regulate glucose homeostasis in human skeletal muscle of healthy and prediabetic subjects exercising in normobaric hypoxia. Seventeen healthy (H; 28.8 ± 2.4 yr; maximal oxygen consumption (V̇O2max): 45.1 ± 1.8 mL·kg-1·min-1) and 15 prediabetic (P; 44.6 ± 3.9 yr; V̇O2max: 30.8 ± 2.5 mL·kg-1·min-1) men were randomly assigned to two groups performing an acute exercise bout (heart rate corresponding to 55% V̇O2max) either in normoxic (NE) or in hypoxic (HE; fraction of inspired oxygen [Formula: see text] 14.0%) conditions. An oral glucose tolerance test (OGTT) was performed in a basal state and after an acute exercise bout. Muscle biopsies from m. vastus lateralis were taken before and after exercise. Venous blood samples were taken at regular intervals before, during, and after exercise. The two groups exercising in hypoxia had a larger area under the curve of blood glucose levels during the OGTT after exercise compared with baseline (H: +11%; P: +4%). Compared with pre-exercise, an increase in p-TBC1D1 Ser237 and in p-AMPK Thr172 was observed postexercise in P NE (+95%; +55%, respectively) and H HE (+91%; +43%, respectively). An increase in p-ACC Ser212 was measured after exercise in all groups (H NE: +228%; P NE: +252%; H HE: +252%; P HE: +208%). Our results show that an acute bout of exercise in hypoxia reduces glucose tolerance in healthy and prediabetic subjects. At a molecular level, some adaptations regulating glucose transport in muscle were found in all groups without associations with glucose tolerance after exercise. The results suggest that hypoxia negatively affects glucose tolerance postexercise through unidentified mechanisms.NEW & NOTEWORTHY The molecular mechanisms involved in glucose tolerance after acute exercise in hypoxia have not yet been elucidated in human. Due to the reversible character of their status, prediabetic individuals are of particular interest for preventing the development of type 2 diabetes. The present study is the first to investigate muscle molecular mechanisms during exercise and glucose metabolism after exercise in prediabetic and healthy subjects exercising in normoxia and normobaric hypoxia.

Acute environmental hypoxia potentiates satellite cell-dependent myogenesis in response to resistance exercise through the inflammation pathway in human.

Acute environmental hypoxia may potentiate muscle hypertrophy in response to resistance training but the mechanisms are still unknown. To this end, twenty subjects performed a 1-leg knee extension session (8 sets of 8 repetitions at 80% 1 repetition maximum, 2-min rest between sets) in normoxic or normobaric hypoxic conditions (FiO2 14%). Muscle biopsies were taken 15 min and 4 hours after exercise in the vastus lateralis of the exercised and the non-exercised legs. Blood samples were taken immediately, 2h and 4h after exercise. In vivo, hypoxic exercise fostered acute inflammation mediated by the TNFα/NF-κB/IL-6/STAT3 (+333%, +194%, + 163% and +50% respectively) pathway, which has been shown to contribute to satellite cells myogenesis. Inflammation activation was followed by skeletal muscle invasion by CD68 (+63%) and CD197 (+152%) positive immune cells, both known to regulate muscle regeneration. The role of hypoxia-induced activation of inflammation in myogenesis was confirmed in vitro. Acute hypoxia promoted myogenesis through increased Myf5 (+300%), MyoD (+88%), myogenin (+1816%) and MRF4 (+489%) mRNA levels in primary myotubes and this response was blunted by siRNA targeting STAT3. In conclusion, our results suggest that hypoxia could improve muscle hypertrophic response following resistance exercise through IL-6/STAT3-dependent myogenesis and immune cells-dependent muscle regeneration.

Regulation of satellite cells by exercise in hypoxic conditions: a narrative review.

PURPOSE: To investigate in vivo the adaptations of satellite cell induced by exercise performed in acute or chronic hypoxic conditions and their contribution to muscle remodeling and hypertrophy. METHODS: Search terms related to exercise, hypoxia and satellite cells were entered on Embase, PubMed and Scopus. Studies were selected for their relevance in terms of regulation of satellite cells by in vivo exercise and muscle contraction in hypoxic conditions. RESULTS: Satellite cell activation and proliferation seem to be enabled after acute hypoxic exercise via regulations induced by myogenic regulatory factors. Several studies reported also a role of the inflammatory pathway nuclear factor-kappa B and angiogenic factors such as vascular endothelial growth factor, both known to upregulate myogenesis. By stimulating angiogenesis, repeated exercise performed in acute hypoxia might contribute to satellite cell activation. Contrary to such exercise conditions, chronic exposure to hypoxia downregulates myogenesis despite the maintenance of physical activity. This impaired myogenesis might be induced by excessive oxidative stress and proteolysis. CONCLUSION: In vivo studies suggest that, in comparison to exercise or hypoxia alone, exercise performed in a hypoxic environment, may improve or impair muscle remodeling induced by contractile activity depending upon the duration of hypoxia. Satellite cells seem to be major actors in these dichotomous adaptations. Further research on the role of angiogenesis, types of contraction and autophagy is needed for a better understanding of their respective role in hypoxic exercise-induced modulations of satellite cell activity in human.

No effect of the endurance training status on senescence despite reduced inflammation in skeletal muscle of older individuals.

The aim of the present study was to determine if the training status decreases inflammation, slows down senescence, and preserves telomere health in skeletal muscle in older compared with younger subjects, with a specific focus on satellite cells. Analyses were conducted on skeletal muscle and cultured satellite cells from vastus lateralis biopsies (n = 34) of male volunteers divided into four groups: young sedentary (YS), young trained cyclists (YT), old sedentary (OS), and old trained cyclists (OT). The senescence state and inflammatory profile were evaluated by telomere dysfunction-induced foci (TIF) quantification, senescence-associated ß-galactosidase (SA-ß-Gal) staining, and quantitative (q)RT-PCR. Independently of the endurance training status, TIF levels (+35%, P < 0.001) and the percentage of SA-ß-Gal-positive cells (+30%, P < 0.05) were higher in cultured satellite cells of older compared with younger subjects. p16 (4- to 5-fold) and p21 (2-fold) mRNA levels in skeletal muscle were higher with age but unchanged by the training status. Aging induced higher CD68 mRNA levels in human skeletal muscle (+102%, P = 0.009). Independently of age, both trained groups had lower IL-8 mRNA levels (-70%, P = 0.011) and tended to have lower TNF-α mRNA levels (-40%, P = 0.10) compared with the sedentary subjects. All together, we found that the endurance training status did not slow down senescence in skeletal muscle and satellite cells in older compared with younger subjects despite reduced inflammation in skeletal muscle. These findings highlight that the link between senescence and inflammation can be disrupted in skeletal muscle.

Cardiotoxin-induced skeletal muscle injury elicits profound changes in anabolic and stress signaling, and muscle fiber type composition.

To improve muscle healing upon injury, it is of importance to understand the interplay of key signaling pathways during muscle regeneration. To study this, mice were injected with cardiotoxin (CTX) or PBS in the Tibialis Anterior muscle and were sacrificed 2, 5 and 12 days upon injection. The time points represent different phases of the regeneration process, i.e. destruction, repair and remodeling, respectively. Two days upon CTX-injection, p-mTORC1 signaling and stress markers such as BiP and p-ERK1/2 were upregulated. Phospho-ERK1/2 and p-mTORC1 peaked at d5, while BiP expression decreased towards PBS levels. Phospho-FOXO decreased 2 and 5 days following CTX-injection, indicative of an increase in catabolic signaling. Furthermore, CTX-injection induced a shift in the fiber type composition, characterized by an initial loss in type IIa fibers at d2 and at d5. At d5, new type IIb fibers appeared, whereas type IIa fibers were recovered at d12. To conclude, CTX-injection severely affected key modulators of muscle metabolism and histology. These data provide useful information for the development of strategies that aim to improve muscle molecular signaling and thereby recovery.

Muscle structural, energetic and functional benefits of endurance exercise training in sickle cell disease.

Sickle cell disease (SCD) patients display skeletal muscle hypotrophy, altered oxidative capacity, exercise intolerance and poor quality of life. We previously demonstrated that moderate-intensity endurance training is beneficial for improving muscle function and quality of life of patients. The present study evaluated the effects of this moderate-intensity endurance training program on skeletal muscle structural and metabolic properties. Of the 40 randomized SCD patients, complete data sets were obtained from 33. The training group (n = 15) followed a personalized moderate-intensity endurance training program, while the non-training (n = 18) group maintained a normal lifestyle. Biopsies of the vastus lateralis muscle and submaximal incremental cycling tests were performed before and after the training program. Endurance training increased type I muscle fiber surface area (P = .038), oxidative enzyme activity [citrate synthase, P < .001; ß-hydroxyacyl-CoA dehydrogenase, P = .009; type-I fiber cytochrome c oxidase, P = .042; respiratory chain complex IV, P = .017] and contents of respiratory chain complexes I (P = .049), III (P = .005), IV (P = .003) and V (P = .002). Respiratory frequency, respiratory exchange ratio, blood lactate concentration and rating of perceived exertion were all lower at a given submaximal power output after training vs non-training group (all P < .05). The muscle content of proteins involved in glucose transport and pH regulation were unchanged in the training group relative to the non-training group. The moderate-intensity endurance exercise program improved exercise capacity and muscle structural and oxidative properties. This trial was registered at www.clinicaltrials.gov as #NCT02571088.

Effects of A High Intensity Interval Session on Mucosal Immune Function and Salivary Hormones in Male and Female Endurance Athletes.

Although the effects of high intensity interval training (HIIT) on health and sports performance are well documented, the effects of this training type on mucosal immune function remain unclear. The aim of this study was to assess the impact of an acute HIIT session on salivary immune and endocrine marker levels (immunoglobulin A (sIgA), alpha amylase (sAA), cortisol (C), and testosterone (T)) in male and female endurance athletes. Twenty subjects (ten males and ten females) underwent ten bouts of treadmill running using a 4 min:2 min work:rest ratio at ~90% of peak oxygen uptake (VO2peak). Saliva samples were collected 5 min before and 20 min post-exercise. During work intervals, female participants had a higher HR than male participants (+4.0 ± 5%; p = 0.008). Rating of perceived exertion (RPE) increased throughout the duration of the HIIT session in both males and females (main time effect: p < 0.001), but was higher in males than females (+17 ± 4%; time x gender main effect: p < 0.001). Lactate concentrations were similar in both males and females. Exercise increased the concentration of salivary IgA (males: +24 ± 6%, p = 0.004; females: +27 ± 3%, p = 0.03), salivary alpha-amylase (males: +44 ± 22%, p = 0.036; females: +71 ± 26%, p = 0.026) and salivary cortisol (males: +41 ± 24%, p = 0.015; females: +55 ± 24%, p = 0.005). Testosterone levels and the Testosterone/Cortisol ratio remained stable in both males and females. These findings suggest that the physiological stress produced by a HIIT session does not affect immune function and does not disturb the anabolic/catabolic balance.

Exercise and the control of muscle mass in human.

During the course of life, muscle mass undergoes many changes in terms of quantity and quality. Skeletal muscle is a dynamic tissue able to hypertrophy or atrophy according to growth, ageing, physical activity, nutrition and health state. The purpose of the present review is to present the mechanisms by which exercise can induce changes in human skeletal muscle mass by modulating protein balance and regulating the fate of satellite cells. Exercise is known to exert transcriptional, translational and post-translational regulations as well as to induce epigenetic modifications and to control messenger RNA stability, which all contribute to the regulation of protein synthesis. Exercise also regulates the autophagy-lysosomal and the ubiquitin-proteasome pathways, the two main proteolytic systems in skeletal muscle, indicating that exercise participates to the regulation of the quality control mechanisms of cellular components and, therefore, to muscle health. Finally, activation, proliferation and differentiation of satellite cells can be enhanced by exercise to induce muscle remodelling and hypertrophy. Each of these mechanisms can potentially impact skeletal muscle mass, depending on the intensity, duration and frequency with which the signal appears.

Activation of protein synthesis, regeneration, and MAPK signaling pathways following repeated bouts of eccentric cycling.

The aim of this study was to examine the activation of skeletal muscle signaling pathways related to protein synthesis and the gene expression of regeneration/degradation markers following repeated bouts of eccentric cycling. Nine untrained men (25.4 ± 1.9 yr) performed two 30-min eccentric cycling bouts (ECC1, ECC2) at 85% of maximal concentric workload, separated by 2 wk. Muscle biopsies were taken from the vastus lateralis before and 2 h after each bout. Indirect markers of muscle damage were assessed before and 24-48 h after exercise. Changes in the Akt/mammalian target of rapamycin (mTOR)/rbosomal protein S6 kinase 1 (S6K1)/ribosomal protein S6 (rpS6) and MAPK signaling pathways were measured by Western blot and changes in mRNA expression of IL-6 and IL-1ß, and myogenic regulatory factors (MRFs) were measured by real-time PCR. ECC1 induced greater increases in indirect markers of muscle damage compared with ECC2. Phosphorylation of S6K1 and rpS6 increased after both exercise bouts (P < 0.05), whereas phosphorylation of mTOR increased after ECC2 only (P = 0.03). Atrogin-1 mRNA expression decreased after ECC1 and ECC2 (P < 0.05) without changes in muscle RING-finger protein-1 mRNA. Basal mRNA levels of myoblast determination protein-1 (MyoD), MRF4, and myogenin were higher 2 wk after ECC1 (P < 0.05). MRF4 mRNA increased after ECC1 and ECC2 (P < 0.05), whereas MyoD mRNA expression increased only after ECC1 (P = 0.03). Phosphorylation of JNK and p38 MAPK increased after both exercise bouts (P < 0.05), similar to IL-6 and IL-1ß mRNA expression. All together, these results suggest that differential regulation of the mTOR pathway and MRF expression could mediate the repeated bout effect observed between an initial and secondary bout of eccentric exercise.

Environmental hypoxia favors myoblast differentiation and fast phenotype but blunts activation of protein synthesis after resistance exercise in human skeletal muscle.

We hypothesized that a single session of resistance exercise performed in moderate hypoxic (FiO2: 14%) environmental conditions would potentiate the anabolic response during the recovery period spent in normoxia. Twenty subjects performed a 1-leg knee extension session in normoxic or hypoxic conditions. Muscle biopsies were taken 15 min and 4 h after exercise in the vastus lateralis of the exercised and the nonexercised legs. Blood and saliva samples were taken at regular intervals before, during, and after the exercise session. The muscle fractional-protein synthetic rate was determined by deuterium incorporation into proteins, and the protein-degradation rate was determined by methylhistidine release from skeletal muscle. We found that: 1) hypoxia blunted the activation of protein synthesis after resistance exercise; 2) hypoxia down-regulated the transcriptional program of autophagy; 3) hypoxia regulated the expression of genes involved in glucose metabolism at rest and the genes involved in myoblast differentiation and fusion and in muscle contraction machinery after exercise; and 4) the hypoxia-inducible factor-1α pathway was not activated at the time points studied. Contrary to our hypothesis, environmental hypoxia did not potentiate the short-term anabolic response after resistance exercise, but it initiated transcriptional regulations that could potentially translate into satellite cell incorporation and higher force production in the long term.-Gnimassou, O., Fernández-Verdejo, R., Brook, M., Naslain, D., Balan, E., Sayda, M., Cegielski, J., Nielens, H., Decottignies, A., Demoulin, J.-B., Smith, K., Atherton, P. J., Fancaux, M., Deldicque, L. Environmental hypoxia favors myoblast differentiation and fast phenotype but blunts activation of protein synthesis after resistance exercise in human skeletal muscle.

Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A Randomized Controlled Trial.

OBJECTIVES: As the catabolic state induced by septic shock together with the physical inactivity of patients lead to the rapid loss of muscle mass and impaired function, the purpose of this study was to test whether an early physical therapy during the onset of septic shock regulates catabolic signals and preserves skeletal muscle mass. DESIGN: Randomized controlled trial. SETTING: Tertiary mixed ICU. PATIENTS: Adult patients admitted for septic shock within the first 72 hours. INTERVENTIONS: Patients were assigned randomly into two groups. The control group benefited from manual mobilization once a day. The intervention group had twice daily sessions of both manual mobilization and 30-minute passive/active cycling therapy. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle biopsies and electrophysiology testing were performed at day 1 and day 7. Muscle biopsies were analyzed for histology and molecular components of signaling pathways regulating protein synthesis and degradation as well as inflammation markers. Hemodynamic values and patient perception were collected during each session. Twenty-one patients were included. Three died before the second muscle biopsy. Ten patients in the control and eight in the intervention group were analyzed. Markers of the catabolic ubiquitin-proteasome pathway, muscle atrophy F-box and muscle ring finger-1 messenger RNA, were reduced at day 7 only in the intervention group, but without difference between groups (muscle atrophy F-box: -7.3% ± 138.4% in control vs -56.4% ± 37.4% in intervention group; p = 0.23 and muscle ring finger-1: -30.8% ± 66.9% in control vs -62.7% ± 45.5% in intervention group; p = 0.15). Muscle fiber cross-sectional area (µm) was preserved by exercise (-25.8% ± 21.6% in control vs 12.4% ± 22.5% in intervention group; p = 0.005). Molecular regulations suggest that the excessive activation of autophagy due to septic shock was lower in the intervention group, without being suppressed. Markers of anabolism and inflammation were not modified by the intervention, which was well tolerated by the patients. CONCLUSIONS: Early physical therapy during the first week of septic shock is safe and preserves muscle fiber cross-sectional area.

Using polyphenol derivatives to prevent muscle wasting.

PURPOSE OF REVIEW: To highlight recent evidence for the ability of polyphenols and their derivatives to reduce muscle wasting in different pathological states. RECENT FINDINGS: From January 2016 to August 2017, four articles dealt with the effects of polyphenols on muscle wasting, which were all carried out in mice. The four studies found that polyphenols reduced muscle mass loss associated with cancer cachexia, acute inflammation or sciatic nerve section. One study even showed that muscle mass was totally preserved when rutin was added to the diet of mice undergoing cancer cachexia. The beneficial effects of polyphenols on muscle wasting were mainly due to a reduction in the activation of the nuclear factor-kappa B pathway, a lower oxidative stress level and a better mitochondrial function. In addition, urolithin B was found to have a testosterone-like effect and to favorably regulate muscle protein balance. SUMMARY: During the last 20 months, additional data have been collected about the beneficial effects of rutin, curcumin, quercetin, ellagitanins and urolithin B to limit the loss of muscle mass associated with several pathological states. However, currently, scientific evidence lacks for their use as nutraceuticals in human.

Activating transcription factor 3 attenuates chemokine and cytokine expression in mouse skeletal muscle after exercise and facilitates molecular adaptation to endurance training.

Activating transcription factor (ATF)3 regulates the expression of inflammation-related genes in several tissues under pathological contexts. In skeletal muscle, atf3 expression increases after exercise, but its target genes remain unknown. We aimed to identify those genes and to determine the influence of ATF3 on muscle adaptation to training. Skeletal muscles of ATF3-knockout (ATF3-KO) and control mice were analyzed at rest, after exercise, and after training. In resting muscles, there was no difference between genotypes in enzymatic activities or fiber type. After exercise, a microarray analysis in quadriceps revealed ATF3 affects genes modulating chemotaxis and chemokine/cytokine activity. Quantitative PCR showed that the mRNA levels of chemokine C-C motif ligand (ccl)8 and chemokine C-X-C motif ligand (cxcl)13 were higher in quadriceps of ATF3-KO mice than in control mice. The same was observed for ccl9 and cxcl13 in soleus. Also in soleus, ccl2, interleukin (il)6, il1ß, and cluster of differentiation (cd)68 mRNA levels increased after exercise only in ATF3-KO mice. Endurance training increased the basal mRNA level of hexokinase-2, hormone sensitive lipase, glutathione peroxidase-1, and myosin heavy chain IIa in quadriceps of control mice but not in ATF3-KO mice. In summary, ATF3 attenuates the expression of inflammation-related genes after exercise and thus facilitates molecular adaptation to training.-Fernández-Verdejo, R., Vanwynsberghe, A. M., Essaghir, A., Demoulin, J.-B., Hai, T., Deldicque, L., Francaux, M. Activating transcription factor 3 attenuates chemokine and cytokine expression in mouse skeletal muscle after exercise and facilitates molecular adaptation to endurance training.

Toll like receptor expression induced by exercise in obesity and metabolic syndrome: A systematic review.

BACKGROUND: Obesity and metabolic syndrome are disorders that correlate with the activation of pro-inflammatory pathways and cytokine production, to which Toll like receptors (TLR) contribute. Exercise may act as an anti-inflammatory modulator, but there is no consensus about the role of the TLR in this tuning. The present styudy aims to systematically review the current evidence on exercise-induced TLR regulation in animals and humans suffering from obesity and metabolic syndrome. METHODS: Pubmed and Scopus databases were searched for publications from 1990 to September 2015. Search terms included: "Toll like Receptor", "TLR", "exercise", "obesity", "diabetes", and "metabolic syndrome". Elegibility criteria comprised: randomized control trials, cross-sectional and cohort studies; human or animal models with metabolic syndrome; any type of exercise; TLR expression measurement in any tissue by a clearly reported technique. The quality of selected studies was assessed using a modified version of the Downs and Black Quality Assessment Checklist. Data of study design; population; exercise type, timing and training elements; measurement technique, tissue analyzed and main outcome were extracted and categorized to facilitate data synthesis. RESULTS: 17 studies were included, of which 11 publications obtained a high, 5 a moderate and 1 a low score for quality assessment. A total of 8 human studies were analyzed: 6 studies used endurance continuous or interval training protocols, 1 study resistance training and the remaining study was performed following a marathon race. Blood cells were analyzed in seven studies, of which four studies sampled peripheral blood mononuclear cells (PBMC), three analyzed whole blood and one study sampled skeletal muscle. Nine animal studies were included: 8 used endurance training and 1 acute aerobic exercise. A variety of tissues samples were explored such as PBMC, skeletal muscle, adipose, vascular and nervous tissue. Globally, the animal studies showed a marked tendency towards a down-regulation of TLR2 and 4 expression accompagnied with, a reduced activation of nuclear factorkappaB (NF-κB) signaling and cytokine production, and an improvement in insulin sensitivity and body composition. CONCLUSION: While animal studies showed a marked tendency towards TLR2 and 4 down-regulation after chronic endurance exercise, the current evidence in human is not sufficiently robust to conclude any role of TLR in the anti-inflammatory properties of exercise.

The effect of a standard whole blood donation on oxygen uptake and exercise capacity: a systematic review and meta-analysis.

BACKGROUND: Blood is a life-saving product for many people worldwide. Voluntary blood donation serves the demand for blood but there are concerns among potential donors about the impact of blood loss on exercise performance. This systematic review aimed to collect the best available evidence of the effect of a standard whole blood donation on aerobic exercise performance. STUDY DESIGN AND METHODS: Studies from six databases dealing with a standard whole blood donation (400-500 mL) followed by (sub)maximal exercise were retained. The outcomes included exercise-related blood variables (hemoglobin [Hb] concentration, hematocrit, and red blood cell count) and endurance exercise variables ((sub)maximal oxygen uptake, peak work rate, and time to exhaustion). Overall effects at different time points postdonation were investigated by performing meta-analyses and calculating mean differences (and 95% confidence intervals). The GRADE methodology (Grades of Recommendation, Assessment, Development, and Evaluation) was used to assess the quality of evidence. RESULTS: We identified 6237 references and finally included 18 before-after studies of low quality. Twenty-four to 48 hours after a blood donation, 1) Hb concentration was reduced (7% decrease) until 14 days after the blood donation (4% decrease), 2) maximal oxygen uptake (VO2max ) was lower (7% decrease), and 3) a reduction in maximal exercise capacity (10% decrease) was present. CONCLUSION: The best available evidence indicates that a standard whole blood donation (400-500 mL) leads to small but potentially physiologically important reductions in Hb levels, VO2max , and maximal exercise capacity in the first 2 days after the blood donation.