A single bout of resistance exercise triggers mitophagy, potentially involving the ejection of mitochondria in human skeletal muscle.

AIM: The present study aimed to investigate the effects of a single bout of resistance exercise on mitophagy in human skeletal muscle (SkM). METHODS: Eight healthy men were recruited to complete an acute bout of one-leg resistance exercise. SkM biopsies were obtained one hour after exercise in the resting leg (Rest-leg) and the contracting leg (Ex-leg). Mitophagy was assessed using protein-related abundance, transmission electron microscopy (TEM), and fluorescence microscopy. RESULTS: Our results show that acute resistance exercise increased pro-fission protein phosphorylation (DRP1Ser616) and decreased mitophagy markers such as PARKIN and BNIP3L/NIX protein abundance in the Ex-leg. Additionally, mitochondrial complex IV decreased in the Ex-leg when compared to the Rest-leg. In the Ex-leg, TEM and immunofluorescence images showed mitochondrial cristae abnormalities, a mitochondrial fission phenotype, and increased mitophagosome-like structures in both subsarcolemmal and intermyofibrillar mitochondria. We also observed increased mitophagosome-like structures on the subsarcolemmal cleft and mitochondria in the extracellular space of SkM in the Ex-leg. We stimulated human primary myotubes with CCCP, which mimics mitophagy induction in the Ex-leg, and found that BNIP3L/NIX protein abundance decreased independently of lysosomal degradation. Finally, in another human cohort, we found a negative association between BNIP3L/NIX protein abundance with both mitophagosome-like structures and mitochondrial cristae density in the SkM. CONCLUSION: The findings suggest that a single bout of resistance exercise can initiate mitophagy, potentially involving mitochondrial ejection, in human skeletal muscle. BNIP3L/NIX is proposed as a sensitive marker for assessing mitophagy flux in SkM.

Effects of Polarized Training on Cardiometabolic Risk Factors in Young Overweight and Obese Women: A Randomized-Controlled Trial.

Introduction: Volume and intensity are major variables governing exercise training-mediated beneficial effects in both athletes and patients. Although polarized endurance training optimizes and maximizes physiological gains in highly trained individuals, its cardiometabolic protective-effects have not been established. The purpose of the present single site, randomized-controlled trial was to compare the effects of 12-weeks of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and polarized volume training (POL) programs on cardiometabolic risk factors in young overweight and obese women. Materials and Methods: A total of 64 overweight/obese young women (age 23.3 ± 3.8 years, body mass index 33.8 ± 3.8 kg/m2) were randomly assigned to four groups: control group (CTRL), polarized volume training group, moderate-intensity endurance training group, and HIIT group. The cardiorespiratory capacity, glycemic and lipid profiles, whole-body substrate utilization, and body composition were assessed before and after the intervention. Results: After the intervention, VO2peak and power output at VO2peak increased in all exercised-groups (time effect: p < 0.0001). Power output at VT1 was increased only in the POL group compared to the CTRL group (p = 0.019). Relative fold changes in fasting plasma glucose concentrations decreased only in POL group (p = 0.002). Training induced a significant increase in relative fat oxidation in all the groups (time effect: p < 0.001). Relative fat oxidation increased only in the POL group compared to the CTRL group (training effect: p = 0.032). Conclusion: Twelve-weeks of polarized volume training showed overall superior effects on cardiorespiratory fitness, basal glycemic control, and substrate oxidation in comparison to MICT and HIIT training modalities. These data suggest that polarized volume training is an effective non-pharmacological treatment strategy for reducing cardiovascular disease risk factors in young overweight and obese women. The trial is registered at ISRCTN, number ISRCTN34421723.

Lactate administration activates the ERK1/2, mTORC1, and AMPK pathways differentially according to skeletal muscle type in mouse.

Skeletal muscle is described as an endocrine organ, constitutively or intermittently secreting bioactive molecules. The signaling pathways by which these molecules mediate changes in skeletal muscle and regulate interorgan crosstalk are only partly understood. Lactate is widely described as a signaling molecule in different cells, but the role of lactate as a signaling molecule in mature skeletal muscle has not been fully unveiled. The aim of this study was to determine the role of lactate on activation of signaling pathways in adult mouse skeletal muscle. Male mice were injected intraperitoneally with lactate or saline, and tissues were dissected after 40 min. Phosphorylation levels of relevant proteins in muscle were assessed by Western blotting. After lactate administration, we found an increase in p-ERK1/2Thr202/Tyr204 (3.5-fold; P = 0.004) and p-p70S6KThr389 (1.9-fold; P = 0.01) in quadriceps; and an increase in p-rpS6Ser235/236 in both quadriceps (6.3-fold; P = 0.01) and EDL (2.3-fold; P = 0.01), without changes in soleus. There was a tendency toward an increase in p-AMPKThr172 (1.7-fold; P = 0.08), with a significant increase in p-ACCSer79 (1.5-fold; P = 0.04) in soleus, without changes in quadriceps and EDL. These results support the hypothesis that lactate plays a role in the molecular signaling related to hypertrophy and to oxidative metabolism on adult skeletal muscle and suggest that this activation depends on the skeletal muscle type. The mechanisms that underlie the effect of lactate in mature skeletal muscles remain to be established.

¿Puede el ejercicio físico per se disminuir el peso corporal en sujetos con sobrepeso/obesidad? / Exercise as a tool to reduce body weight

The prevalence of overweight and obesity is increasing, creating a public health problem. The loss of approximately 10% of body weight is recommended to reduce the risk of mortality associated with metabolic diseases and to increase the quality of life in adults with overweight or obesity. Non-pharmacological strategies used for weight management are caloric restriction and physical exercise. Nevertheless, the independent effect of physical exercise to decrease body weight is unclear, and could be responsible for only 20% of the weight loss when healthy lifestyles are prescribed. However, exercise has other benefits for health, independent of its weight reducing effect. In fact, physical inactivity is responsible for twice the deaths caused by obesity. The aim of this review is to discuss the importance of physical exercise in the reduction of body weight in subjects with overweight or obesity.

NOX2 Inhibition Impairs Early Muscle Gene Expression Induced by a Single Exercise Bout.

Reactive oxygen species (ROS) participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2) in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg) or vehicle for 3 days, were swim-exercised for 60 min. Phospho-p47(phox) levels were significantly upregulated by exercise in flexor digitorum brevis (FDB). Moreover, exercise significantly increased NOX2 complex assembly (p47(phox)-gp91(phox) interaction) demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx), citrate synthase (CS), mitochondrial transcription factor A (tfam) and interleukin-6 (IL-I6) in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p < 0.001). These results were corroborated using gp91-dstat in an in vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.

Reactive oxygen species and calcium signals in skeletal muscle: A crosstalk involved in both normal signaling and disease.

Reactive Oxygen Species (ROS) have been profusely studied as agents of potential damage to living cells and they have been related to a number of pathological processes. Increasing evidence points to a more positive role of ROS in cell signaling and the detailed mechanism that regulates the precise amount of ROS needed for cell functioning without the deleterious effects of excess ROS still needs to be resolved in detail. In skeletal muscle the main source of ROS during normal functioning appears to be NADPH oxidase 2 (NOX2), which is activated by electrical stimuli (or exercise) through a cascade of events that include ATP release through pannexin1 channels. NOX2 is a protein complex that assembles in the T-tubule membrane before activation and ROS production by NOX2 appears to be important for muscle adaptation through gene expression and mitochondrial biogenesis as well as for improving glucose transport after insulin action. Excess ROS production (or diminished antioxidant defenses) plays a role in a number of pathological processes in skeletal muscle. Together with increased reactive nitrogen species, an increase in ROS appears to have a deleterious role in a model of Duchenne muscular dystrophy as well as muscle wasting in other diseases such as aging sarcopenia and cancer cachexia. In addition, ROS is involved in obesity and muscle insulin resistance, both of which are causally related to type 2 diabetes. A detailed description of the fine-tuning of ROS (including all sources of ROS) in skeletal muscle in health and disease will significantly contribute to our knowledge of both muscle adaptation and muscle related pathologies.

Effects of plyometric training on maximal-intensity exercise and endurance in male and female soccer players.

In a randomised controlled trial design, effects of 6 weeks of plyometric training on maximal-intensity exercise and endurance performance were compared in male and female soccer players. Young (age 21.1 ± 2.7 years) players with similar training load and competitive background were assigned to training (women, n = 19; men, n = 21) and control (women, n = 19; men, n = 21) groups. Players were evaluated for lower- and upper-body maximal-intensity exercise, 30 m sprint, change of direction speed and endurance performance before and after 6 weeks of training. After intervention, the control groups did not change, whereas both training groups improved jumps (effect size (ES) = 0.35-1.76), throwing (ES = 0.62-0.78), sprint (ES = 0.86-1.44), change of direction speed (ES = 0.46-0.85) and endurance performance (ES = 0.42-0.62). There were no differences in performance improvements between the plyometric training groups. Both plyometric groups improved more in all performance tests than the controls. The results suggest that adaptations to plyometric training do not differ between men and women.

Effects of Exercise Training under Hyperbaric Oxygen on Oxidative Stress Markers and Endurance Performance in Young Soccer Players: A Pilot Study.

The aim of the present study was to determine the effects of three weeks of hyperbaric oxygen (HBO2) training on oxidative stress markers and endurance performance in young soccer players. Participants (18.6 ± 1.6 years) were randomized into hyperbaric-hyperoxic (HH) training (n = 6) and normobaric normoxic (NN) training (n = 6) groups. Immediately before and after the 5th, 10th, and 15th training sessions, plasma oxidative stress markers (lipid hydroperoxides and uric acid), plasma antioxidant capacity (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid [TROLOX]), arterial blood gases, acid-base balance, bases excess (BE), and blood lactate analyses were performed. Before and after intervention, maximal oxygen uptake (VO2max) and peak power output (PPO) were determined. Neither HH nor NN experienced significant changes on oxidative stress markers or antioxidant capacity during intervention. VO2max and PPO were improved (moderate effect size) after HH training. The results suggest that HBO2 endurance training does not increase oxidative stress markers and improves endurance performance in young soccer players. Our findings warrant future investigation to corroborate that HBO2 endurance training could be a potential training approach for highly competitive young soccer players.

Altered ROS production, NF-κB activation and interleukin-6 gene expression induced by electrical stimulation in dystrophic mdx skeletal muscle cells.

Duchenne muscular dystrophy is a fatal X-linked genetic disease, caused by mutations in the dystrophin gene, which cause functional loss of this protein. This pathology is associated with an increased production of reactive oxygen (ROS) and nitrogen species. The aim of this work was to study the alterations in NF-κB activation and interleukin-6 (IL-6) expression induced by membrane depolarization in dystrophic mdx myotubes. Membrane depolarization elicited by electrical stimulation increased p65 phosphorylation, NF-κB transcriptional activity and NF-κB-dependent IL-6 expression in wt myotubes, whereas in mdx myotubes it had the opposite effect. We have previously shown that depolarization-induced intracellular Ca2+ increases and ROS production are necessary for NF-κB activation and stimulation of gene expression in wt myotubes. Dystrophic myotubes showed a reduced amplitude and area under the curve of the Ca2+ transient elicited by electrical stimulation. On the other hand, electrical stimuli induced higher ROS production in mdx than wt myotubes, which were blocked by NOX2 inhibitors. Moreover, mRNA expression and protein levels of the NADPH oxidase subunits: p47phox and gp91phox were increased in mdx myotubes. Looking at ROS-dependence of NF-κB activation we found that in wt myotubes external administration of 50 µM H2O2 increased NF-κB activity; after administration of 100 and 200 µM H2O2 there was no effect. In mdx myotubes there was a dose-dependent reduction in NF-κB activity in response to external administration of H2O2, with a significant effect of 100 µM and 200 µM, suggesting that ROS levels are critical for NF-κB activity. Prior blockage with NOX2 inhibitors blunted the effects of electrical stimuli in both NF-κB activation and IL-6 expression. Finally, to ascertain whether stimulation of NF-κB and IL-6 gene expression by the inflammatory pathway is also impaired in mdx myotubes, we studied the effect of lipopolysaccharide on both NF-κB activation and IL-6 expression. Exposure to lipopolysaccharide induced a dramatic increase in both NF-κB activation and IL-6 expression in both wt and mdx myotubes, suggesting that the altered IL-6 gene expression after electrical stimulation in mdx muscle cells is due to dysregulation of Ca2+ release and ROS production, both of which impinge on NF-κB signaling. IL-6 is a key metabolic modulator that is released by the skeletal muscle to coordinate a multi-systemic response (liver, muscle, and adipocytes) during physical exercise; the alteration of this response in dystrophic muscles may contribute to an abnormal response to contraction and exercise.

[Eight weeks of combined high intensity intermittent exercise normalized altered metabolic parameters in women]. / ¿Pueden ocho semanas de ejercicio físico combinado normalizar marcadores metabólicos de sujetos hiperglicémicos y dislipidémicos?

BACKGROUND: Short term physical training programs may improve insulin resistance and hyperglycemia. AIM: To assess the effects of eight weeks of combined exercise program on serum lipids and glycemic level in women with hyperglycemia and hypercholesterolemia. PATIENTS AND METHODS: Ten healthy women, nine women with hyperglycemia, ten with hypercholesterolemia and nine with hyperglycemia/hypercholesterolemia were studied. Participants were subjected to eight weeks into a program of combined physical exercise (high intensity interval + resistance training). RESULTS: Fasting glycemia decreased by 12 and 14% in hyperglycemic and hyperglycemic/hypercholesterolemic participants, respectively. Serum insulin decreased in all groups in a range from 27 to 37%. HOMA IR for insulin resistance decreased similarly. A significant decrease in TC and TG was observed only in those altered baseline subjects. CONCLUSIONS: Eight weeks of combined physical exercise had a favorable effect on insulin resistance in this group of women.

The effects of interset rest on adaptation to 7 weeks of explosive training in young soccer players.

The aim of the study was to compare the effects of plyometric training using 30, 60, or 120 s of rest between sets on explosive adaptations in young soccer players. Four groups of athletes (age 10.4 ± 2.3 y; soccer experience 3.3 ± 1.5 y) were randomly formed: control (CG; n = 15), plyometric training with 30 s (G30; n = 13), 60 s (G60; n = 14), and 120 s (G120; n = 12) of rest between training sets. Before and after intervention players were measured in jump ability, 20-m sprint time, change of direction speed (CODS), and kicking performance. The training program was applied during 7 weeks, 2 sessions per week, for a total of 840 jumps. After intervention the G30, G60 and G120 groups showed a significant (p = 0.0001 - 0.04) and small to moderate effect size (ES) improvement in the countermovement jump (ES = 0.49; 0.58; 0.55), 20 cm drop jump reactive strength index (ES = 0.81; 0.89; 0.86), CODS (ES = -1.03; -0.87; -1.04), and kicking performance (ES = 0.39; 0.49; 0.43), with no differences between treatments. The study shows that 30, 60, and 120 s of rest between sets ensure similar significant and small to moderate ES improvement in jump, CODS, and kicking performance during high-intensity short-term explosive training in young male soccer players. Key pointsReplacing some soccer drills by low volume high-intensity plyometric training would be beneficial in jumping, change of direction speed, and kicking ability in young soccer players.A rest period of 30, 60 or 120 seconds between low-volume high-intensity plyometric sets would induce significant and similar explosive adaptations during a short-term training period in young soccer players.Data from this research can be helpful for soccer trainers in choosing efficient drills and characteristics of between sets recovery programs to enhance performances in young male soccer players.

¿Pueden ocho semanas de ejercicio físico combinado normalizar marcadores metabólicos de sujetos hiperglicémicos y dislipidémicos? / Eight weeks of combined high intensity intermittent exercise normalized altered metabolic parameters in women

Background: Short term physical training programs may improve insulin resistance and hyperglycemia. Aim: To assess the effects of eight weeks of combined exercise program on serum lipids and glycemic level in women with hyperglycemia and hypercholesterolemia. Patients and Methods: Ten healthy women, nine women with hyperglycemia, ten with hypercholesterolemia and nine with hyperglycemia/hypercholesterolemia were studied. Participants were subjected to eight weeks into a program of combined physical exercise (high intensity interval + resistance training). Results: Fasting glycemia decreased by 12 and 14% in hyperglycemic and hyperglycemic/hypercholesterolemic participants, respectively. Serum insulin decreased in all groups in a range from 27 to 37%. HOMA IR for insulin resistance decreased similarly. A significant decrease in TC and TG was observed only in those altered baseline subjects. Conclusions: Eight weeks of combined physical exercise had a favorable effect on insulin resistance in this group of women.

Respuestas metabólicas inducidas por ejercicio físico de alta intensidad en mujeres sedentarias con glicemia basal alterada e hipercolesterolemia / Metabolic response to high intensity exercise training in sedentary hyperglycemic and hypercholesterolemic women

Background: High intensity training could be an effective way of improving health on individuals at high metabolic risk. Aim: To investigate the effects of a high intensity training intervention on metabolic-related markers in sedentary women at high metabolic risk. Material and Methods: Forty six sedentary women with a body mass index (BMI) over 25 kg/m² were assigned to four groups, according to their metabolic profile; hyperglycemia (H, n = 12), hyperglycemia/hypercholesterolemia (HH, n = 13), normoglycemia (N, n = 10) and normoglycemia/hypercholesterolemia (NH, n = 11). For 12 weeks and five days per week, subjects performed seven intervals of high intensity training (20 to 30 seconds) during a training session of 20 minutes. Anthropometric (body weight, body mass index (BMI), waist circumference) and metabolic variables (glucose, total cholesterol, LDL, HDL and TG) were measured at baseline, at 6 and 12 weeks of intervention. Results: BMI and waist circumference decreased significantly after 12 weeks of intervention. Similarly, glucose decreased significantly after 12 weeks of intervention in all groups. The reduction was of higher magnitude in those groups with hyperglycemia (H = -16%, HH = -22%, N = -7,5%, NH = -9,6%). However, lipid profile (TG, total cholesterol, LDL and HDL) improved significantly only in the hypercholesterolemic groups. Conclusions: Physical activity programs incorporating high intensity training can improve glucose and lipid profile in women with metabolic disorders. Moreover, this benefit is greatest in those individuals with highest metabolic burden.

Regional fat changes induced by localized muscle endurance resistance training.

The purpose of this study was to examine the effects of a localized muscle endurance resistance training program on total body and regional tissue composition. Seven men and 4 women (aged 23 ± 1 years) were trained with their nondominant leg during 12 weeks, 3 sessions per week. Each session consisted of 1 set of 960-1,200 repetitions (leg press exercise), at 10-30% 1 repetition maximum. Before and after training, body mass, bone mass, bone mineral density (BMD), lean mass, fat mass, and fat percentage were determined by dual-emission x-ray absorptiometry. Energy intakes were registered using a food recall questionnaire. At the whole-body level, body mass, bone mass, BMD, lean mass, or body fat percentage were not significantly changed. However, body fat mass significantly decreased by 5.1% (preexercise: 13.5 ± 6.3 kg; postexercise: 12.8 ± 5.4 kg, p < 0.05). No significant changes in bone mass, lean mass, fat mass, or fat percentage were observed in both the control and trained leg. A significant (p < 0.05) decrease in fat mass was observed in the upper extremities and trunk (10.2 and 6.9%, respectively, p < 0.05). The reduction of fat mass in the upper extremities and trunk was significantly greater (p < 0.05) than the fat mass change observed in the trained leg but not in the control leg. No significant changes were observed in energy intake pre- and postexercise intervention (2,646 ± 444 kcal·d-1 and 2,677 ± 617 kcal·d-1, respectively). In conclusion, the training program was effective in reducing fat mass, but this reduction was not achieved in the trained body segment. The present results expand the limited knowledge available about the plastic heterogeneity of regional body tissues when a localized resistance training program is applied.

[Metabolic response to high intensity exercise training in sedentary hyperglycemic and hypercholesterolemic women]. / Respuestas metabólicas inducidas por ejercicio físico de alta intensidad en mujeres sedentarias con glicemia basal alterada e hipercolesterolemia.

BACKGROUND: High intensity training could be an effective way of improving health on individuals at high metabolic risk. AIM: To investigate the effects of a high intensity training intervention on metabolic-related markers in sedentary women at high metabolic risk. MATERIAL AND METHODS: Forty six sedentary women with a body mass index (BMI) over 25 kg/m² were assigned to four groups, according to their metabolic profile; hyperglycemia (H, n = 12), hyperglycemia/hypercholesterolemia (HH, n = 13), normoglycemia (N, n = 10) and normoglycemia/hypercholesterolemia (NH, n = 11). For 12 weeks and five days per week, subjects performed seven intervals of high intensity training (20 to 30 seconds) during a training session of 20 minutes. Anthropometric (body weight, body mass index (BMI), waist circumference) and metabolic variables (glucose, total cholesterol, LDL, HDL and TG) were measured at baseline, at 6 and 12 weeks of intervention. RESULTS: BMI and waist circumference decreased significantly after 12 weeks of intervention. Similarly, glucose decreased significantly after 12 weeks of intervention in all groups. The reduction was of higher magnitude in those groups with hyperglycemia (H = -16%, HH = -22%, N = -7,5%, NH = -9,6%). However, lipid profile (TG, total cholesterol, LDL and HDL) improved significantly only in the hypercholesterolemic groups. CONCLUSIONS: Physical activity programs incorporating high intensity training can improve glucose and lipid profile in women with metabolic disorders. Moreover, this benefit is greatest in those individuals with highest metabolic burden.