The role of muscle disuse in muscular and cardiovascular fitness: A systematic review and meta-regression.

We aimed to assess the effects of muscle disuse on muscle strength (MS), muscle mass (MM) and cardiovascular fitness. Databases were scrutinized to identify human studies assessing the effects of muscle disuse on both (1) MM and (2) maximal oxygen uptake (VO2max) and/or MS. Random-effects meta-analysis and meta-regression with initial physical fitness and length of the protocol as a priori determined moderators were performed. We quantitatively analyzed 51 different studies, and the level of significance was set at p < 0.05. Data from the participants in 14 studies showed a decline in both VO2max (SMD: -0.93; 95% CI: -1.27 to -0.58) and MM (SMD: -0.34; 95% CI: -0.57 to -0.10). Data from 47 studies showed a decline in strength (-0.88; 95% CI: -1.04 to -0.73) and mass (SMD: -0.47; 95% CI: -0.58 to -0.36). MS loss was twice as high as MM loss, but differences existed between anatomical regions. Notably, meta-regression analysis revealed that initial MS was inversely associated with MS decline. VO2max and MS decline to a higher extent than MM during muscle disuse. We reported a more profound strength loss in subjects with high muscular strength. This is physiologically relevant for athletes because their required muscular strength can profoundly decline during a period of muscle disuse. It should however be noted that a period of muscle disuse can have devastating consequences in old subjects with low muscular strength.

The Effects of Acute Deep Seawater Supplementation on Muscle Function after Triathlon.

(1) Background: Trainers and athletes have always sought to reduce the failure of muscle function during long endurance events. However, nowadays, it is a topic that is generating much debate in the scientific field. Currently, deep-sea water (DSW) intake seems to be a suitable hydration alternative for this type of endurance event. Therefore, the aim of this study was to determine whether DSW consumption during a triathlon event could preserve muscle function after exercise. (2) Methods: Nineteen trained male triathletes (age = 39.0 ± 4.25 years; BMI = 23.67 ± 1.81 kg/m2) randomly performed three triathlons, one of them consuming DSW (Totum SPORT 30 AB, Laboratories Quinton International, S.L., Spain), the other consuming isotonic placebo and the last with tap water-hydration. A vertical jump test with countermovement and an isometric muscle strength test were conducted before and after the triathlon test. (3) Results: There was a significant difference between treatment × time during the isometric muscle strength test. Based on the Tukey post hoc analysis, the peak net force decreased statistically in the placebo (p = 0.045) and control conditions (p = 0.026), but not in the experimental condition (p = 0.121). In addition, all of the conditions studied obtained similar results in the countermovement vertical jump after exercise. (4) Conclusions: As a result, consumption of DSW seems to delay the failure of muscle function specifically in isometric exercises but does not improve performance in sports. Thus, DSW does not alter muscle capacity in a negative way; therefore, its consumption may be recommended.

Early heart and skeletal muscle mitochondrial response to a moderate hypobaric hypoxia environment.

In eukaryotic cells, aerobic energy is produced by mitochondria through oxygen uptake. However, little is known about the early mitochondrial responses to moderate hypobaric hypoxia (MHH) in highly metabolic active tissues. Here, we describe the mitochondrial responses to acute MHH in the heart and skeletal muscle. Rats were randomly allocated into a normoxia control group (n = 10) and a hypoxia group (n = 30), divided into three groups (0, 6, and 24 h post-MHH). The normoxia situation was recapitulated at the University of Granada, at 662 m above sea level. The MHH situation was performed at the High-Performance Altitude Training Centre of Sierra Nevada located in Granada at 2320 m above sea level. We found a significant increase in mitochondrial supercomplex assembly in the heart as soon as the animals reached 2320 m above sea level and their levels are maintained 24 h post-exposure, but not in skeletal muscle. Furthermore, in skeletal muscle, at 0 and 6 h, there was increased dynamin-related protein 1 (Drp1) expression and a significant reduction in Mitofusin 2. In conclusion, mitochondria from the muscle and heart respond differently to MHH: mitochondrial supercomplexes increase in the heart, whereas, in skeletal muscle, the mitochondrial pro-fission response is trigged. Considering that skeletal muscle was not actively involved in the ascent when the heart was beating faster to compensate for the hypobaric, hypoxic conditions, we speculate that the different responses to MHH are a result of the different energetic requirements of the tissues upon MHH. KEY POINTS: The heart and the skeletal muscle showed different mitochondrial responses to moderate hypobaric hypoxia. Moderate hypobaric hypoxia increases the assembly of the electron transport chain complexes into supercomplexes in the heart. Skeletal muscle shows an early mitochondrial pro-fission response following exposure to moderate hypobaric hypoxia.

Metabolic Adaptations to Morning Versus Afternoon Training: A Systematic Review and Meta-analysis.

BACKGROUND: Some physiological responses such as circulating glucose as well as muscle performance show a circadian rhythmicity. In the present study we aimed to quantitatively synthesize the data comparing the metabolic adaptations induced by morning and afternoon training. METHODS: PubMed, SCOPUS, and Web of Science databases were systematically searched for studies comparing the metabolic adaptations (> 2 weeks) between morning and afternoon training. A meta-analysis was performed using random-effects models with DerSimonian-Laird methods for fasting blood glucose, hemoglobin A1c (HbAc1), homeostatic model assessment (HOMA), insulin, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). RESULTS: We identified 9 studies with 11 different populations (n = 450 participants). We found that afternoon exercise was more effective at reducing circulating triglycerides [standardized mean difference (SMD) - 0.32; 95% confidence interval (CI) - 0.616 to - 0.025] than morning training. Moreover, afternoon tended to decrease fasting blood glucose (SMD - 0.24; 95% CI - 0.478 to 0.004) to a greater extent than morning training. CONCLUSION: Metabolic adaptations to exercise may be dependent on the time of day. Morning training does not show superior effects to afternoon exercise in any of the analyzed outcomes. However, afternoon training is more effective at reducing circulating triglyceride levels and perhaps at reducing fasting blood glucose than morning training. The study was preregistered at PROSPERO (CRD42021287860).

Mitochondrial Function and Signaling to Regulate Cellular Life.

Mitochondria are essential organelles found in nearly all eukaryotic cells, responsible for producing the energy that drives cellular processes [...].

Mitochondrial adaptations to calorie restriction and bariatric surgery in human skeletal muscle: a systematic review with meta-analysis.

OBJECTIVE: We performed a meta-analysis to determine the changes induced by calorie restriction (CR) and bariatric surgery on human skeletal muscle mitochondria. METHODS: A systematic search of Medline and Web of Science was conducted. Controlled trials exploring CR (≥14 days) and mitochondrial function and/or content assessment were included. Moreover, studies analyzing weight loss following gastric surgery were included for comparison purposes. Human muscle data from 28 studies assessing CR (520 muscle samples) and from 10 studies assessing bariatric surgery (155 muscle samples) were analyzed in a random effect meta-analysis with three a priori chosen covariates. MAIN RESULTS: We report a decrease (p < 0.05) (mean (95 % CI)) in maximal mitochondrial state 3 respiration in response to CR (-0.44 (-0.85, -0.03)) but not in response to surgery (-0.33 (-1.18, 0.52)). No changes in mitochondrial content were reported after CR (-0.05 (-0.12, 0.13)) or in response to surgery (0.23 (-0.05, 0.52)). Moreover, data from CR subjects showed a reduction in complex IV (CIV) activity (-0.29 (-0.56, -0.03)) but not in CIV content (-0.21 (-0.63, 0.22)). Similar results were obtained when the length of the protocol, the initial body mass index, and the estimated energy deficit were included in the model as covariates. CONCLUSION: The observation of reduced maximal mitochondrial state 3, uncoupled respiration, and CIV activity without altering mitochondrial content suggests that, in human skeletal muscle, CR mainly modulates intrinsic mitochondrial function.

Does Hypoxia and Stress Erythropoiesis Compromise Cardiac Function in Healthy Adults? A Randomized Trial.

OBJECTIVES: To investigate whether recombinant human erythropoietin (rHuEPO) injections during an altitude training camp impact heart function. METHODS: Thirty (12 women) moderately trained subjects stayed at 2320 m altitude for 4 weeks while training. Subjects were randomized to placebo (isotonic saline) or rHuEPO (20 IU/kg body weight) i.v. injections. Transthoracic echocardiography imaging was acquired 3 days after arrival to altitude and prior to the first placebo or rHuEPO injection as well as one day after the last rHuEPO injection three weeks later. RESULTS: rHuEPO did not alter cardiovascular morphology parameters, systolic or diastolic function. In the placebo group, altitude exposure improved left ventricle (LV) systolic function due to an increased twist angle but rHuEPO had no additional effects. Pulmonary arterial systolic pressure was unaffected in either group. Notably, rHuEPO hampered LV untwist rate without affecting LV early filling. CONCLUSION: rHuEPO provided during mild altitude exposure does not cause any major effects on heart function. The observed alteration in LV untwist induced by rHuEPO is unlikely to have a meaningful clinical effect. Trial Registration Registered on www. CLINICALTRIALS: gov (NCT04227665).

Physiological Benefits and Performance of Sea Water Ingestion for Athletes in Endurance Events: A Systematic Review.

In different endurance events, athletes have limited access to fluid intake, such as ultra-endurance running. For this reason, it is necessary to establish an adequate hydration strategy for this type of long-duration sporting event. Indeed, it seems that the intake of seawater is a suitable hydration alternative to improve post-exercise recovery in this type of endurance event. This seawater is characterized by being a deep natural mineral water of moderate mineralization, which is usually extracted from a depth of about 700 m. Therefore, the aim of this systematic review is to evaluate the efficacy of seawater consumption in both performance and post-exercise recovery in long-duration sport events. A systematic and comprehensive literature search was performed in PubMed, Scopus, and Web of Science in September 2022. Initially, 8 out of 558 articles met the inclusion criteria. Among these eight studies, six were randomized clinical trials, and two were observational studies (one cross-sectional and one prospective study in well-conditioned student athletes). The results showed that deep sea water consumption accelerated the recovery of aerobic capacity and leg muscle capacity on running performance. In addition, the lactate production after the running exercise in seawater was significantly lower than in pure water. In conclusion, the present review demonstrates that seawater consumption could significantly improve the capacity of recovery after exercise.

Seawater Hydration Modulates IL-6 and Apelin Production during Triathlon Events: A Crossover Randomized Study.

A triathlon is an endurance event in which athletes need an efficient hydration strategy since hydration is restricted at different stages. However, it seems that seawater intake can be a suitable hydration alternative for this type of endurance event. Therefore, the aim of this study was to evaluate the efficacy of seawater hydration during a triathlon on cytokine production. Fifteen trained male triathletes (age = 38.8 ± 5.62 years old; BMI = 22.58 ± 2.51 kg/m2) randomly performed three triathlons, one of them consuming seawater (Totum SPORT, Laboratories Quinton International, S.L., Valencia, Spain), the other one consuming tap water ad libitum, and the last a physiologic saline solution as placebo. The triathlon consisted of an 800 m swim, a 90 km bike ride, and a 10 km run. Blood samples were taken at rest and after training, where markers of inflammation, hemoglobin, and hematocrit concentration were assessed. While the seawater was not ergogenic, it significantly increased the release of IL-6 and apelin post-exercise. However, no differences were found between the fractalkine, IL-15, EPO, osteonectin, myostatin, oncostatin, irisin, FSTL1, osteocrin, BDNF, and FGF-21 values over those of the placebo group. The present study demonstrates that hydration with seawater stimulates myokine production, which could lead to improved performance recovery after exercise.

Food made us human: Recent genetic variability and its relevance to the current distribution of macronutrients.

Numerous dietary strategies are currently used for the prevention of metabolic diseases and for weight loss. Some of the strategies that are used do not have an appropriate physiological-nutritional basis and do not take into account the genetic changes that have occurred recently. Thus, in certain cases, they can be harmful to human health. This review aims to explain the genetic mutations that have occurred during human evolution from the first hominids to Homo sapiens and to explain how they have influenced the way we feed ourselves. Some mutations favored brain development and others are related to the digestion of nutrients such as lactose and starch. The influence of the domestication of food and the practice of cooking on human nutrition is also explained. In addition, this review intends to justify the current recommendations on the caloric distribution of macronutrients based on the important influence of genetic changes and adaptations that have occurred in our species.

Physiological Doses of Hydroxytyrosol Modulate Gene Expression in Skeletal Muscle of Exercised Rats.

We tested whether physiological doses of hydroxytyrosol (HT) may alter the mRNA transcription of key metabolic genes in exercised skeletal muscle. Two groups of exercise-trained Wistar rats, HTlow and HTmid, were supplemented with 0.31 and 4.61 mg/kg/d of HT, respectively, for 10 weeks. Another two groups of rats were not supplemented with HT; one remained sedentary and the other one was exercised. After the experimental period, the soleus muscle was removed for qRT-PCR and western blot analysis. The consumption of 4.61 mg/kg/d of HT during exercise increased the mRNA expression of important metabolic proteins. Specifically, 4.61 mg/kg/d of HT may upregulate long-chain fatty acid oxidation, lactate, and glucose oxidation as well as mitochondrial Krebs cycle in trained skeletal muscle. However, a 4.61 mg/kg/d of HT may alter protein translation, as in spite of the increment showed by CD36 and GLUT4 at the mRNA level this was not translated to higher protein content.

Assessment of the Phytochemical and Nutrimental Composition of Dark Chia Seed (Salvia hispánica L.).

Chia seeds are rich sources of different macro and micronutrients associated with health benefits; thus, they may be considered as a functional food. However, the composition depends on the variety, origin, climate and soil. Here, we show a comprehensive characterization of extractable and non-extractable phenolic compounds of dark chia seed Salvia hispanica L. using high-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight (HPLC-ESI-QTOF) and discuss potential health benefits associated with the presence of a number of nutritional and bioactive compounds. We report that dark chia from Jalisco is a high-fiber food, containing omega-3 polyunsaturated fatty acids, essential amino acids (phenylalanine and tryptophan), and nucleosides (adenosine, guanidine and uridine), and rich in antioxidant phenolic compounds, mainly caffeic acid metabolites. Our data suggest that chia seeds may be used as ingredients for the development of functional foods and dietary supplements.

Differential inflammatory response of men and women subjected to an acute resistance exercise.

BACKGROUND: The purpose of this study was to investigate the inflammatory response, lipid peroxidation and muscle damage in men and women athletes subjected to an acute resistance exercise. METHODS: Twenty college athletes (10 men and 10 women) performed a half-squat exercise consisting of five incremental intensities: 20%, 40%, 60%, 80% and 100% of the one-repetition maximum. Blood samples were collected at rest, 15 min and 24 h post-test. The concentration of lipid peroxidation markers and the activities of a skeletal muscle damage marker and a cardiac muscle damage marker were determined in serum. Serum α-actin was measured as a marker of sarcomere damage. Serum levels of interleukin-6, interleukin-10, and tumor necrosis factor alpha were determined to assess the inflammatory response. RESULTS: Interleukin-6 levels were higher at 24 h post-test than at rest and 15 min post-test in men (p < 0.05). Moreover, men showed significantly higher hydroperoxide levels in response to resistance exercise at 24 h post-test than at 15 min post-test (p < 0.05). No differences were found in muscle damage parameters regardless of sex or the time point of the test. No differences regarding the studied variables were found when comparing among different time points in women. CONCLUSION: Our results show a larger influence of half-squat exercises on the release of IL6 and on lipid peroxidation in men than in women at equivalent workloads.

Corrigendum to "Stay Fit, Stay Young: Mitochondria in Movement: The Role of Exercise in the New Mitochondrial Paradigm".

[This corrects the article DOI: 10.1155/2019/7058350.].

Mitochondrial Functionality in Inflammatory Pathology-Modulatory Role of Physical Activity.

The incidence and severity of metabolic diseases can be reduced by introducing healthy lifestyle habits including moderate exercise. A common observation in age-related metabolic diseases is an increment in systemic inflammation (the so-called inflammaging) where mitochondrial reactive oxygen species (ROS) production may have a key role. Exercise prevents these metabolic pathologies, at least in part, due to its ability to alter immunometabolism, e.g., reducing systemic inflammation and by improving immune cell metabolism. Here, we review how exercise regulates immunometabolism within contracting muscles. In fact, we discuss how circulating and resident macrophages alter their function due to mitochondrial signaling, and we propose how these effects can be triggered within skeletal muscle in response to exercise. Finally, we also describe how exercise-induced mitochondrial adaptations can help to fight against virus infection. Moreover, the fact that moderate exercise increases circulating immune cells must be taken into account by public health agencies, as it may help prevent virus spread. This is of interest in order to face not only acute respiratory-related coronavirus (SARS-CoV) responsible for the COVID-19 pandemic but also for future virus infection challenges.

Hydroxytyrosol modifies skeletal muscle GLUT4/AKT/Rac1 axis in trained rats.

Training induces a number of healthy effects including a rise in skeletal muscle (SKM) glucose uptake. These adaptations are at least in part due to the reactive oxygen species produced within SKM, which is in agreement with the notion that antioxidant supplementation blunts some training-induced adaptations. Here, we tested whether hydroxytyrosol (HT), the main polyphenol of olive oil, would modify the molecular regulators of glucose uptake when HT is supplemented during exercise. Rats were included into sedentary and exercised (EXE) groups. EXE group was further divided into a group consuming a low HT dose (0.31 mg·kg·d; EXElow), a moderate HT dose (4.61 mg·kg·d; EXEmid), and a control group (EXE). EXE raised glucose transporter type 4 (GLUT4) protein content, Ras-related C3 botulinum toxin substrate 1 (Rac1) activity, and protein kinase b (AKT) phosphorylation in SKM. Furthermore, EXElow blunted GLUT4 protein content and AKT phosphorylation while EXEmid showed a downregulation of the GLUT4/AKT/Rac1 axis. Hence, a low-to-moderate dose of HT, when it is supplemented as an isolated compound, might alter the beneficial effect of training on basal AKT phosphorylation and Rac1 activity in rats.

Functional role of respiratory supercomplexes in mice: SCAF1 relevance and segmentation of the Qpool.

Mitochondrial respiratory complexes assemble into supercomplexes (SC). Q-respirasome (III2 + IV) requires the supercomplex assembly factor (SCAF1) protein. The role of this factor in the N-respirasome (I + III2 + IV) and the physiological role of SCs are controversial. Here, we study C57BL/6J mice harboring nonfunctional SCAF1, the full knockout for SCAF1, or the wild-type version of the protein and found that exercise performance is SCAF1 dependent. By combining quantitative data-independent proteomics, 2D Blue native gel electrophoresis, and functional analysis of enriched respirasome fractions, we show that SCAF1 confers structural attachment between III2 and IV within the N-respirasome, increases NADH-dependent respiration, and reduces reactive oxygen species (ROS). Furthermore, the expression of AOX in cells and mice confirms that CI-CIII superassembly segments the CoQ in two pools and modulates CI-NADH oxidative capacity.

The emerging role of skeletal muscle mitochondrial dynamics in exercise and ageing.

Mitochondria are the hub for energy production within living cells. They can undergo morphological changes in response to nutrient availability and cellular stress. Here, we review how exercise chronically and acutely affects mitochondrial dynamics. Moreover, we discuss whether mitochondrial dysfunction observed in elderly subjects is due to the ageing process per se or due to the associated sedentary state. Finally, we study how endurance exercise can improve mitochondrial dynamics in older subjects, thereby improving their overall health and likely limiting muscle waste.

Acute/Subacute and Sub-Chronic Oral Toxicity of a Hidroxytyrosol-Rich Virgin Olive Oil Extract.

The objective of this study was to determine the acute (one single dose), subacute (14 days), and sub-chronic (90 days) toxicity of an aqueous virgin olive oil (VOO) extract rich in hydroxytyrosol in rats. For acute/subacute toxicity, rats were divided into three groups. The control group received distilled water (n = 9), another experimental group received a single dose of 300 mg/kg (n = 3), and a third group received one dose of 2000 mg/kg (n = 4) during 14 days. The sub-chronic study included 60rats distributed in three groups (n = 20: 10 males and 10 females) receiving daily different three doses of the VOO extract in the drinking water during 90 days: (1) 100 mg/kg, (2) 300 mg/kg, and (3) 1000 mg/kg. In parallel, a fourth additional group (n = 20: 10 males and 10 females) did not receive any extract (control group). Clinical signs, body weight, functional observations of sensory and motor reactivity, hematological and biochemical analyses, and macroscopic and microscopic histopathology were evaluated. No adverse effects were observed after the administration of the different doses of the hydroxytyrosol-rich VOO extract, which suggests that the enrichment of VOO in its phenolic compound is safe, and can be used as functional foods for the treatment of chronic degenerative diseases.

Human muscular mitochondrial fusion in athletes during exercise.

The main objective of this work was to investigate whether mitochondrial fusion occurs in the skeletal muscle of well-trained athletes in response to high-intensity exercise. Well-trained swimmers (n = 9) performed a duration-matched sprint interval training (SIT) and high-intensity high-volume training (HIHVT) session on separate days. Muscle samples from triceps brachii were taken before, immediately after, and 3 h after the training sessions. Transmission electron microscopy (TEM) was applied to assess mitochondrial morphology. Moreover, expression of genes coding for regulators of mitochondrial fusion and fission were assessed by real-time quantitative PCR. In addition, mitofusin (MFN)2 and optic atrophy 1 (OPA1) were quantified by Western blot analysis. TEM analyses showed that mitochondrial morphology remained altered for 3 h after HIHVT, whereas SIT-induced changes were only evident immediately after exercise. Only SIT increased MFN1 and MFN2 mRNA expression, whereas SIT and HIHVT both increased MFN2 protein content 3 h after exercise. Notably, only HIHVT increased OPA1 protein content. Mitochondrial morphologic changes that suggest fusion occurs in well-adapted athletes during exercise. However, HIHVT appears as a more robust inducer of mitochondrial fusion events than SIT. Indeed, SIT induces a rapid and transient change in mitochondrial morphology.-Huertas, J. R., Ruiz-Ojeda, F. J., Plaza-Díaz, J., Nordsborg, N. B., Martín-Albo, J., Rueda-Robles, A., Casuso, R. A. Human muscular mitochondrial fusion in athletes during exercise.