Systemic Inflammation but not Oxidative Stress Is Associated with Physical Performance in Moderate Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) patients manifest muscle dysfunction and impaired muscle oxidative capacity, which result in reduced exercise capacity and poor health status. The aim of this study was to compare the physical performance, systemic inflammation, and oxidative stress of patients with moderate COPD, and to associate physical performance with inflammatory and oxidative stress plasma markers. Twenty CONTROL (n = 10) and moderate COPD (n = 10) patients participated in this study. Systematic inflammation and oxidative stress plasma markers, maximal aerobic capacity (VO2peak), and maximal isometric strength (MVIC) of the knee extensor (KE) muscles were measured. VO2peak was 31.3% greater in CONTROL compared to COPD (P = 0.006). The MVIC strength of the KE was 43.9% greater in CONTROL compared to COPD (P = 0.002). Tumor necrosis factor-alpha (TNF-α) was 79.6% greater in COPD compared to CONTROL (P < 0.001). Glutathione peroxidase activity (GPx) activity was 27.5% lesser in COPD compared to CONTROL (P = 0.05). TNF-α concentration was correlated with KE MVC strength (R = -0.48; P = 0.045) and VO2peak (R = -0.58; P = 0.01). Meanwhile, malondialdehyde (MDA) and GPx activity were not associated with KE strength or VO2peak (P = 0.74 and P = 0.14, respectively). COPD patients showed lesser muscle strength and aerobic capacity than healthy control individuals. Furthermore, patients with COPD showed greater systemic inflammation and lesser antioxidant capacity than healthy counterparts. A moderate association was evident between levels of systemic inflammation and physical performance variables.

Community strategies for health promotion and prevention of chronic non-communicable diseases with a focus on physical activity and nutrition: the URO/FOCOS study protocol.

Non-communicable diseases (NCDs) account for 71% of all annual deaths, totaling 41 million people worldwide. The development and progression of these diseases are highly related to the environment and lifestyle choices, among which physical inactivity and excess malnutrition stand out. Currently, in Chile, there is no evidence at the regional and local level on the impact of physical activity and healthy nutrition plans and interventions on health promotion, prevention, and timely treatment of NCDs. The following protocol delineates the URO/FOCOS (Universidad Regional de O'Higgins/FOrtaleciendo COmunidades Saludables- Regional University of O'Higgins/Strengthening Healthy Communities) study, which will assess pilot community intervention strategies using a participatory action research approach by identifying barriers and facilitators on the practice of physical activity and healthy eating habits. In this project, the community from the O'Higgins region will be involved throughout the entire research process to develop strategies that promote regular physical activity and healthy eating practices. We propose three interrelated strategies: (1) Participatory Action Research, (2) Community interventions for promoting physical activity and healthy nutrition practices, and (3) health education. The URO/FOCOS study offers a unique opportunity in the O'Higgins region to develop participatory strategies and interventions based on the community's needs and motivations with regard to physical activity and healthy eating habits. We believe these strategies will help to improve the community's overall health through effective changes in their decision and preferences toward a more active lifestyle and healthier nutrition practices.

Relative lipid oxidation associates directly with mitochondrial fusion phenotype and mitochondria-sarcoplasmic reticulum interactions in human skeletal muscle.

Disturbances in skeletal muscle lipid oxidation might induce ectopic fat deposition and lipotoxicity. Nevertheless, the cellular mechanisms that regulate skeletal muscle lipid oxidation have not been fully determined. We aimed to determine whether there was an association between relative whole body lipid oxidation and mitochondrial size or mitochondria-sarcoplasmic reticulum interactions in the skeletal muscle. Twelve healthy men were included [mean (standard deviation), 24.7 (1.5) yr old, 24.4 (2.6) kg/m2]. The respiratory quotient (RQ) was used to estimate relative lipid oxidation at rest and during exercise (50% maximal oxygen consumption, 600 kcal expended). A skeletal muscle biopsy was obtained from the vastus lateralis at rest. Transmission electron microscopy was used to determine mitochondrial size and mitochondria-sarcoplasmic reticulum interactions (≤50 nm of distance between organelles). Protein levels of fusion/fission regulators were measured in skeletal muscle by Western blot. Resting RQ and exercise RQ associated inversely with intermyofibrillar mitochondrial size (r = -0.66 and r = -0.60, respectively, P < 0.05). Resting RQ also associated inversely with the percentage of intermyofibrillar mitochondria-sarcoplasmic reticulum interactions (r = -0.62, P = 0.03). Finally, intermyofibrillar mitochondrial size associated inversely with lipid droplet density (r = -0.66, P = 0.01) but directly with mitochondria fusion-to-fission ratio (r = 0.61, P = 0.03). Our results show that whole body lipid oxidation is associated with skeletal muscle intermyofibrillar mitochondrial size, fusion phenotype, and mitochondria-sarcoplasmic-reticulum interactions in nondiabetic humans.

Resting metabolic rate and skeletal muscle SERCA and Na+ /K+ ATPase activities are not affected by fish oil supplementation in healthy older adults.

Omega-3 polyunsaturated fatty acids (PUFAs) have unique properties purported to influence several aspects of metabolism, including energy expenditure and protein function. Supplementing with n-3 PUFAs may increase whole-body resting metabolic rate (RMR), by enhancing Na+ /K+ ATPase (NKA) activity and reducing the efficiency of sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) activity by inducing a Ca2+ leak-pump cycle. The purpose of this study was to examine the effects of fish oil (FO) on RMR, substrate oxidation, and skeletal muscle SERCA and NKA pump function in healthy older individuals. Subjects (n = 16 females; n = 8 males; 65 ± 1 years) were randomly assigned into groups supplemented with either olive oil (OO) (5 g/day) or FO (5 g/day) containing 2 g/day eicosapentaenoic acid and 1 g/day docosahexaenoic acid for 12 weeks. Participants visited the laboratory for RMR and substrate oxidation measurements after an overnight fast at weeks 0 and 12. Skeletal muscle biopsies were taken during weeks 0 and 12 for analysis of NKA and SERCA function and protein content. There was a main effect of time with decrease in RMR (5%) and fat oxidation (18%) in both the supplementation groups. The kinetic parameters of SERCA and NKA maximal activity, as well as the expression of SR and NKA proteins, were not affected after OO and FO supplementation. In conclusion, these results suggest that FO supplementation is not effective in altering RMR, substrate oxidation, and skeletal muscle SERCA and NKA protein levels and activities, in healthy older men and women.

Assessment of Na+/K+ ATPase Activity in Small Rodent and Human Skeletal Muscle Samples.

INTRODUCTION: In skeletal muscle, the Na/K ATPase (NKA) plays essential roles in processes linked to muscle contraction, fatigue, and energy metabolism; however, very little information exists regarding the regulation of NKA activity. The scarcity of information regarding NKA function in skeletal muscle likely stems from methodological constraints, as NKA contributes minimally to total cellular ATP utilization, and therefore contamination from other ATPases prevents the assessment of NKA activity in muscle homogenates. Here we introduce a method that improves accuracy and feasibility for the determination of NKA activity in small rodent muscle samples (5-10 mg) and in human skeletal muscle. METHODS: Skeletal muscle homogenates from mice (n = 6) and humans (n = 3) were used to measure NKA and sarcoplasmic reticulum Ca ATPase (SERCA) activities with the addition of specific ATPase inhibitors to minimize "background noise." RESULTS: We observed that myosin ATPase activity was the major interfering factor for estimation of NKA activity in skeletal muscle homogenates, as the addition of 25 µM of blebbistatin, a specific myosin ATPase inhibitor, considerably minimized "background noise" (threefold) and enabled the determination of NKA maximal activity with values three times higher than previously reported. The specificity of the assay was demonstrated after the addition of 2 mM ouabain, which completely inhibited NKA. On the other hand, the addition of blebbistatin did not affect the ability to measure SERCA function. The coefficient of variation for NKA and SERCA assays were 6.2% and 4.4%, respectively. CONCLUSION: The present study has improved the methodology to determine NKA activity. We further show the feasibility of measuring NKA and SERCA activities from a common muscle homogenate. This methodology is expected to aid in our long-term understanding of how NKA affects skeletal muscle metabolic homeostasis and contractile function in diverse situations.

Basal Serum Cortisol and Testosterone/Cortisol Ratio Are Related to Rate of Na+ Lost During Exercise in Elite Soccer Players.

During exercise, the human body maintains optimal body temperature through thermoregulatory sweating, which implies the loss of water, sodium (Na+), and other electrolytes. Sweat rate and sweat Na+ concentration show high interindividual variability, even in individuals exercising under similar conditions. Testosterone and cortisol may regulate sweat Na+ loss by modifying the expression/activity of the cystic fibrosis transmembrane conductance regulator. This has not been tested. As a first approximation, the authors aimed to determine whether basal serum concentrations of testosterone or cortisol, or the testosterone/cortisol ratio relate to sweat Na+ loss during exercise. A total of 22 male elite soccer players participated in the study. Testosterone and cortisol were measured in blood samples before exercise (basal). Sweat samples were collected during a training session, and sweat Na+ concentration was determined. The basal serum concentrations of testosterone and cortisol and their ratio were (mean [SD]) 13.6 (3.3) pg/ml, 228.9 (41.4) ng/ml, and 0.06 (0.02), respectively. During exercise, the rate of Na+ loss was related to cortisol (r = .43; p < .05) and to the testosterone/cortisol ratio (r = -.46; p < .01), independently of the sweating rate. The results suggest that cortisol and the testosterone/cortisol ratio may influence Na+ loss during exercise. It is unknown whether this regulation depends on the cystic fibrosis transmembrane conductance regulator.

Incorporation of Omega-3 Fatty Acids Into Human Skeletal Muscle Sarcolemmal and Mitochondrial Membranes Following 12 Weeks of Fish Oil Supplementation.

Fish oil (FO) supplementation in humans results in the incorporation of omega-3 fatty acids (FAs) eicosapentaenoic acid (EPA; C20:5) and docosahexaenoic acid (DHA; C20:6) into skeletal muscle membranes. However, despite the importance of membrane composition in structure-function relationships, a paucity of information exists regarding how different muscle membranes/organelles respond to FO supplementation. Therefore, the purpose of the present study was to determine the effects 12 weeks of FO supplementation (3g EPA/2g DHA daily) on the phospholipid composition of sarcolemmal and mitochondrial fractions, as well as whole muscle responses, in healthy young males. FO supplementation increased the total phospholipid content in whole muscle (57%; p < 0.05) and the sarcolemma (38%; p = 0.05), but did not alter the content in mitochondria. The content of omega-3 FAs, EPA and DHA, were increased (+3-fold) in whole muscle, and mitochondrial membranes, and as a result the omega-6/omega-3 ratios were dramatically decreased (-3-fold), while conversely the unsaturation indexes were increased. Intriguingly, before supplementation the unsaturation index (UI) of sarcolemmal membranes was ∼3 times lower (p < 0.001) than either whole muscle or mitochondrial membranes. While supplementation also increased DHA within sarcolemmal membranes, EPA was not altered, and as a result the omega-6/omega-3 ratio and UI of these membranes were not altered. All together, these data revealed that mitochondrial and sarcolemmal membranes display unique phospholipid compositions and responses to FO supplementation.

Lack of effects of fish oil supplementation for 12 weeks on resting metabolic rate and substrate oxidation in healthy young men: A randomized controlled trial.

Fish oil (FO) has been shown to have beneficial effects in the body via incorporation into the membranes of many tissues. It has been proposed that omega-3 fatty acids in FO may increase whole body resting metabolic rate (RMR) and fatty acid (FA) oxidation in human subjects, but the results to date are equivocal. The purpose of this study was to investigate the effects of a 12 week FO supplementation period on RMR and substrate oxidation, in comparison to an olive oil (OO) control group, in young healthy males (n = 26; 22.8 ± 2.6 yr). Subjects were matched for age, RMR, physical activity, VO2max and body mass, and were randomly separated into a group supplemented with either OO (3 g/d) or FO containing 2 g/d eicosapentaenoic acid (EPA) and 1 g/d docosahexaenoic acid (DHA). Participants visited the lab for RMR and substrate oxidation measurements after an overnight fast (10-12 hr) at weeks 0, 6 and 12. Fasted blood samples were taken at baseline and after 12 weeks of supplementation. There were significant increases in the EPA (413%) and DHA (59%) levels in red blood cells after FO supplementation, with no change of these fatty acids in the OO group. RMR and substrate oxidation did not change after supplementation with OO or FO after 6 and 12 weeks. Since there was no effect of supplementation on metabolic measures, we pooled the two treatment groups to determine whether there was a seasonal effect on RMR and substrate oxidation. During the winter season, there was an increase in FA oxidation (36%) with a concomitant decrease (34%) in carbohydrate (CHO) oxidation (p < 0.01), with no change in RMR. These measures were unaffected during the summer season. In conclusion, FO supplementation had no effect on RMR and substrate oxidation in healthy young males. Resting FA oxidation was increased and CHO oxidation reduced over a 12 week period in the winter, with no change in RMR. TRIAL REGISTRATION: ClinicalTrials.gov NCT02092649.