The role of microRNAs in regulating inflammation and exercise-induced adaptations in rheumatoid arthritis.

MicroRNAs (miRNAs) are endogenously generated single-stranded RNAs that play crucial roles in numerous biological processes, such as cell development, proliferation, differentiation, metabolism and apoptosis. They negatively regulate target gene expression by repressing translation of messenger RNA into a functional protein. Several miRNAs have been implicated in the development and progression of RA. They are involved in inflammatory and immune processes and are associated with susceptibility to RA and disease activity. They are also considered to be potential markers of disease activity or even therapeutic targets. Likewise, several miRNAs are affected acutely by exercise and regulate exercise-related adaptations in the skeletal muscle and cardiovascular system and aerobic fitness. Interestingly, some miRNAs affected by exercise are also important in the context of RA. Investigating these might increase our understanding of the effects of exercise in RA and improve exercise prescription and, potentially, disease management. In this review, we focus on the miRNAs that are associated with both RA and exercise and discuss their roles in (and potential interactions between) RA and exercise-induced adaptations.

ROBITT: A tool for assessing the risk-of-bias in studies of temporal trends in ecology.

Aggregated species occurrence and abundance data from disparate sources are increasingly accessible to ecologists for the analysis of temporal trends in biodiversity. However, sampling biases relevant to any given research question are often poorly explored and infrequently reported; this can undermine statistical inference. In other disciplines, it is common for researchers to complete 'risk-of-bias' assessments to expose and document the potential for biases to undermine conclusions. The huge growth in available data, and recent controversies surrounding their use to infer temporal trends, indicate that similar assessments are urgently needed in ecology.We introduce ROBITT, a structured tool for assessing the 'Risk-Of-Bias In studies of Temporal Trends in ecology'. ROBITT has a similar format to its counterparts in other disciplines: it comprises signalling questions designed to elicit information on the potential for bias in key study domains. In answering these, users will define study inferential goal(s) and relevant statistical target populations. This information is used to assess potential sampling biases across domains relevant to the research question (e.g. geography, taxonomy, environment), and how these vary through time. If assessments indicate biases, then users must clearly describe them and/or explain what mitigating action will be taken.Everything that users need to complete a ROBITT assessment is provided: the tool, a guidance document and a worked example. Following other disciplines, the tool and guidance document were developed through a consensus-forming process across experts working in relevant areas of ecology and evidence synthesis.We propose that researchers should be strongly encouraged to include a ROBITT assessment when publishing studies of biodiversity trends, especially when using aggregated data. This will help researchers to structure their thinking, clearly acknowledge potential sampling issues, highlight where expert consultation is required and provide an opportunity to describe data checks that might go unreported. ROBITT will also enable reviewers, editors and readers to establish how well research conclusions are supported given a dataset combined with some analytical approach. In turn, it should strengthen evidence-based policy and practice, reduce differing interpretations of data and provide a clearer picture of the uncertainties associated with our understanding of reality.

Acute effects of exercise on pain symptoms, clinical inflammatory markers and inflammatory cytokines in people with rheumatoid arthritis: a systematic literature review.

Background: Exercise is advocated in the treatment of rheumatoid arthritis (RA). However, uncertainty around the acute effects of exercise on pain and inflammation may be stopping people with RA from exercising more regularly. Objectives: To determine the acute effects of exercise on pain symptoms, clinical inflammatory markers, and inflammatory cytokines in RA. Design: A systematic review of the literature. Data sources and methods: Five databases were searched (PubMed, Cochrane Library, CINAHL, Scopus and SPORTDiscus); inclusion criteria were studies with acute exercise, a definite diagnosis of RA and disease characteristics assessed by clinical function (i.e., disease activity score, health assessment questionnaire and self-reported pain), clinical markers associated with inflammation (i.e., c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), and inflammatory cytokines (i.e., interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)). Results: From a total of 1544 articles, initial screening and full text assessment left 11 studies meeting the inclusion criteria. A total of 274 people were included in the studies (RA = 186; control = 88). Acute bouts of aerobic, resistance, and combined aerobic and resistance exercise did not appear to exacerbate pain symptoms in people with RA. Conclusion: Post-exercise responses for pain, clinical inflammatory markers and inflammatory cytokines were not different between people with or without RA. Exercise prescription was variable between studies, which limited between-study comparisons. Therefore, future investigations in people with RA are warranted, which combine different exercise modes and intensities to examine acute effects on pain symptoms and inflammatory markers. Registration: The PROSPERO international prospective register of systematic reviews - CRD42018091155.

Participation in physical activity decreased more in people with rheumatoid arthritis than the general population during the COVID-19 lockdown: a cross-sectional study.

The COVID-19 pandemic and social distancing restrictions have significantly reduced population-wide physical activity (PA) levels. However, the impact of the pandemic and relevant restrictions on PA participation, and any potential barriers to it, in people with rheumatoid arthritis (RA) are not clear. Furthermore, we are unsure if any such PA changes have affected their body weight, mental wellbeing, and/or quality of life (QoL). Thus, the aim of this study was to examine the impact of the lockdown on PA participation in people with RA, versus people without RA. Participants (n = 128; RA = 27, non-RA = 101) completed a self-administered online survey, which included questions on PA, body weight, mental wellbeing and QoL. PA participation during lockdown was significantly lower among RA versus non-RA participants (p < 0.001). Additionally, a similar profile of results was found where more RA participants vs non-RA participants reported reduced habitual PA (59% vs 33%) and increased body weight (59% vs 35%). Mental wellbeing scores were similarly low in both groups during lockdown (RA: 20.8 ± 4.2; non-RA: 22.2 ± 3.4, p = 0.080). Matched group comparisons identified similar trends to full sample analyses. In the first months of the lockdown, more people with RA reported decreased PA participation and increased body weight than their non-RA counterparts. Access to exercise equipment and facilities appears to be the main cause for these results. Looking beyond COVID-19, specific PA promotion for people with RA will be required to prevent a pandemic of inactivity.

Glucose and Fructose Hydrogel Enhances Running Performance, Exogenous Carbohydrate Oxidation, and Gastrointestinal Tolerance.

PURPOSE: Beneficial effects of carbohydrate (CHO) ingestion on exogenous CHO oxidation and endurance performance require a well-functioning gastrointestinal (GI) tract. However, GI complaints are common during endurance running. This study investigated the effect of a CHO solution-containing sodium alginate and pectin (hydrogel) on endurance running performance, exogenous and endogenous CHO oxidation, and GI symptoms. METHODS: Eleven trained male runners, using a randomized, double-blind design, completed three 120-min steady-state runs at 68% V˙O2max, followed by a 5-km time-trial. Participants ingested 90 g·h-1 of 2:1 glucose-fructose (13C enriched) as a CHO hydrogel, a standard CHO solution (nonhydrogel), or a CHO-free placebo during the 120 min. Fat oxidation, total and exogenous CHO oxidation, plasma glucose oxidation, and endogenous glucose oxidation from liver and muscle glycogen were calculated using indirect calorimetry and isotope ratio mass spectrometry. GI symptoms were recorded throughout the trial. RESULTS: Time-trial performance was 7.6% and 5.6% faster after hydrogel ([min:s] 19:29 ± 2:24, P < 0.001) and nonhydrogel (19:54 ± 2:23, P = 0.002), respectively, versus placebo (21:05 ± 2:34). Time-trial performance after hydrogel was 2.1% faster (P = 0.033) than nonhydrogel. Absolute and relative exogenous CHO oxidation was greater with hydrogel (68.6 ± 10.8 g, 31.9% ± 2.7%; P = 0.01) versus nonhydrogel (63.4 ± 8.1 g, 29.3% ± 2.0%; P = 0.003). Absolute and relative endogenous CHO oxidation was lower in both CHO conditions compared with placebo (P < 0.001), with no difference between CHO conditions. Absolute and relative liver glucose oxidation and muscle glycogen oxidation were not different between CHO conditions. Total GI symptoms were not different between hydrogel and placebo, but GI symptoms were higher in nonhydrogel compared with placebo and hydrogel (P < 0.001). CONCLUSION: The ingestion of glucose and fructose in hydrogel form during running benefited endurance performance, exogenous CHO oxidation, and GI symptoms compared with a standard CHO solution.

Splenic responses to a series of repeated maximal static and dynamic apnoeas with whole-body immersion in water.

NEW FINDINGS: What is the central question of this study? Splenic contractions occur in response to apnoea-induced hypoxia with and without face immersion in water. However, the splenic responses to a series of static or dynamic apnoeas with whole-body water immersion in non-divers and elite breath-hold divers are unknown. What is the main finding and its importance? Static and dynamic apnoeas were equally effective in stimulating splenic contractions across non-divers and elite breath-hold divers. These findings demonstrate that the magnitude of the splenic response is largely dictated by the degree of the hypoxemic stress encountered during voluntary apnoeic epochs. ABSTRACT: Splenic contractions occur in response to apnoea-induced hypoxia with and without facial water immersion. However, the splenic responses to a series of static (STA) or dynamic (DYN) apnoeas with whole-body water immersion in non-divers (NDs) and elite breath-hold divers (EBHDs) are unknown. EBHD (n = 8), ND (n = 10) and control participants (n = 8) were recruited. EBHD and ND performed a series of five maximal DYN or STA on separate occasions. Control performed a static eupnoeic (STE) protocol to control against any effects of water immersion and diurnal variation on splenic volume and haematology. Heart rate (HR) and peripheral oxygen saturation (SpO2 ) were monitored for 30 s after each apnoea. Pre- and post-apnoeic splenic volumes were quantified ultrasonically, and blood samples were drawn for haematology. For EBHD and ND end-apnoeic HR was higher (P < 0.001) and SpO2 was lower in DYN (P = 0.024) versus STA. EBHD attained lower end-apnoeic SpO2 during DYN and STA than NDs (P < 0.001). Splenic contractions occurred following DYN (EBHD, -47 ± 6%; ND, -37 ± 4%; P < 0.001) and STA (EBHD, -26 ± 4%; ND, -26 ± 8%; P < 0.01). DYN-associated splenic contractions were greater than STA in EBHD only (P = 0.042). Haemoglobin concentrations were higher following DYN only (EBHD, +5 ± 8g/L  , +4 ± 2%; ND, +8 ± 3 g/L , +4.9 ± 3%; P = 0.019). Haematocrit remained unchanged after each protocol. There were no between group differences in post-apnoeic splenic volume or haematology. In both groups, splenic contractions occurred in response to STA and DYN when combined with whole-body immersion. DYN apnoeas, were effective at increasing haemoglobin concentrations but not STA apnoeas. Thus, the magnitude of the splenic response relates to the hypoxemic stress encountered during apnoeic epochs.

Six weeks of dynamic apnoeic training stimulates erythropoiesis but does not increase splenic volume.

PURPOSE: This study examined the influence of dynamic apnoea training on splenic volume and haematological responses in non-breath-hold divers (BHD). METHODS: Eight non-BHD performed ten maximal dynamic apnoeas, four times a week for  six weeks. Splenic volumes were assessed ultrasonically, and blood samples were drawn for full blood count analysis, erythropoietin, iron, ferritin, albumin, protein and osmolality at baseline, 24 h post the completion of each week's training sessions and seven days post the completion of the training programme. Additionally, blood samples were drawn for haematology at 30, 90, and 180 min post session one, twelve and twenty-four. RESULTS: Erythropoietin was only higher than baseline (6.62 ± 3.03 mlU/mL) post session one, at 90 (9.20 ± 1.88 mlU/mL, p = 0.048) and 180 min (9.04 ± 2.35 mlU/mL, p = 0.046). Iron increased from baseline (18 ± 3 µmol/L) post week five (23 ± 2 µmol/L, p = 0.033) and six (21 ± 6 µmol/L; p = 0.041), whereas ferritin was observed to be lower than baseline (111 ± 82 µg/L) post week five (95 ± 75 µg/L; p = 0.016), six (84 ± 74 µg/L; p = 0.012) and one week post-training (81 ± 63 µg/L; p = 0.008). Reticulocytes increased from baseline (57 ± 12 × 109/L) post week one (72 ± 17 × 109/L, p = 0.037) and six (71 ± 17 × 109/L, p = 0.021) while no changes were recorded in erythrocytes (p = 0.336), haemoglobin (p = 0.124) and splenic volumes (p = 0.357). CONCLUSIONS: Six weeks of dynamic apnoeic training increase reticulocytes without altering mature erythrocyte concentration and splenic volume.

Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial.

We investigated the effects of ingesting a leucine-enriched essential amino acid (EAA) gel alone or combined with resistance exercise (RE) versus RE alone (control) on plasma aminoacidemia and intramyocellular anabolic signaling in healthy younger (28 ± 4 years) and older (71 ± 3 years) adults. Blood samples were obtained throughout the three trials, while muscle biopsies were collected in the postabsorptive state and 2 h following RE, following the consumption of two 50 mL EAA gels (40% leucine, 15 g total EAA), and following RE with EAA (combination (COM)). Protein content and the phosphorylation status of key anabolic signaling proteins were determined via immunoblotting. Irrespective of age, during EAA and COM peak leucinemia (younger: 454 ± 32 µM and 537 ± 111 µM; older: 417 ± 99 µM and 553 ± 136 µM) occurred ~60-120 min post-ingestion (younger: 66 ± 6 min and 120 ± 60 min; older: 90 ± 13 min and 78 ± 12 min). In the pooled sample, the area under the curve for plasma leucine and the sum of branched-chain amino acids was significantly greater in EAA and COM compared with RE. For intramyocellular signaling, significant main effects were found for condition (mTOR (Ser2481), rpS6 (Ser235/236)) and age (S6K1 (Thr421/Ser424), 4E-BP1 (Thr37/46)) in age group analyses. The phosphorylation of rpS6 was of similar magnitude (~8-fold) in pooled and age group data 2 h following COM. Our findings suggest that a gel-based, leucine-enriched EAA supplement is associated with aminoacidemia and a muscle anabolic signaling response, thus representing an effective means of stimulating muscle protein anabolism in younger and older adults following EAA and COM.

Erythropoietic responses to a series of repeated maximal dynamic and static apnoeas in elite and non-breath-hold divers.

PURPOSE: Serum erythropoietin (EPO) concentration is increased following static apnoea-induced hypoxia. However, the acute erythropoietic responses to a series of dynamic apnoeas in non-divers (ND) or elite breath-hold divers (EBHD) are unknown. METHODS: Participants were stratified into EBHD (n = 8), ND (n = 10) and control (n = 8) groups. On two separate occasions, EBHD and ND performed a series of five maximal dynamic apnoeas (DYN) or two sets of five maximal static apnoeas (STA). Control performed a static eupnoeic (STE) protocol to control against any effects of water immersion and diurnal variation on EPO. Peripheral oxygen saturation (SpO2) levels were monitored up to 30 s post each maximal effort. Blood samples were collected at 30, 90, and 180 min after each protocol for EPO, haemoglobin and haematocrit concentrations. RESULTS: No between group differences were observed at baseline (p > 0.05). For EBHD and ND, mean end-apnoea SpO2 was lower in DYN (EBHD, 62 ± 10%, p = 0.024; ND, 85 ± 6%; p = 0.020) than STA (EBHD, 76 ± 7%; ND, 96 ± 1%) and control (98 ± 1%) protocols. EBHD attained lower end-apnoeic SpO2 during DYN and STA than ND (p < 0.001). Serum EPO increased from baseline following the DYN protocol in EBHD only (EBHD, p < 0.001; ND, p = 0.622). EBHD EPO increased from baseline (6.85 ± 0.9mlU/mL) by 60% at 30 min (10.82 ± 2.5mlU/mL, p = 0.017) and 63% at 180 min (10.87 ± 2.1mlU/mL, p = 0.024). Serum EPO did not change after the STA (EBHD, p = 0.534; ND, p = 0.850) and STE (p = 0.056) protocols. There was a significant negative correlation (r = - 0.49, p = 0.003) between end-apnoeic SpO2 and peak post-apnoeic serum EPO concentrations. CONCLUSIONS: The novel findings demonstrate that circulating EPO is only increased after DYN in EBHD. This may relate to the greater hypoxemia achieved by EBHD during the DYN.

Skeletal muscle, haematological and splenic volume characteristics of elite breath-hold divers.

PURPOSE: The aim of the study was to provide an evaluation of the oxygen transport, exchange and storage capacity of elite breath-hold divers (EBHD) compared with non-divers (ND). METHODS: Twenty-one healthy males' (11 EBHD; 10 ND) resting splenic volumes were assessed by ultrasound and venous blood drawn for full blood count analysis. Percutaneous skeletal muscle biopsies were obtained from the m. vastus lateralis to measure capillarisation, and fibre type-specific localisation and distribution of myoglobin and mitochondrial content using quantitative immunofluorescence microscopy. RESULTS: Splenic volume was not different between groups. Reticulocytes, red blood cells and haemoglobin concentrations were higher (+ 24%, p < 0.05; + 9%, p < 0.05; + 3%, p < 0.05; respectively) and mean cell volume was lower (- 6.5%, p < 0.05) in the EBHD compared with ND. Haematocrit was not different between groups. Capillary density was greater (+ 19%; p < 0.05) in the EBHD. The diffusion distance (R95) was lower in type I versus type II fibres for both groups (EBHD, p < 0.01; ND, p < 0.001), with a lower R95 for type I fibres in the EBHD versus ND (- 13%, p < 0.05). Myoglobin content was higher in type I than type II fibres in EBHD (+ 27%; p < 0.01) and higher in the type I fibres of EBHD than ND (+ 27%; p < 0.05). No fibre type differences in myoglobin content were observed in ND. Mitochondrial content was higher in type I than type II fibres in EBHD (+ 35%; p < 0.05), with no fibre type differences in ND or between groups. CONCLUSIONS: In conclusion, EBDH demonstrate enhanced oxygen storage in both blood and skeletal muscle and a more efficient oxygen exchange capacity between blood and skeletal muscle versus ND.

Cold spot microrefugia hold the key to survival for Brazil's Critically Endangered Araucaria tree.

Brazil's Araucaria tree (Araucaria angustifolia) is an iconic living fossil and a defining element of the Atlantic Forest global biodiversity hotspot. But despite more than two millennia as a cultural icon in southern Brazil, Araucaria is on the brink of extinction, having lost 97% of its extent to 20th-century logging. Although logging is now illegal, 21st-century climate change constitutes a new-but so far unevaluated-threat to Araucaria's future survival. We use a robust ensemble modelling approach, using recently developed climate data, high-resolution topography and fine-scale vegetation maps, to predict the species' response to climate change and its implications for conservation on meso- and microclimate scales. We show that climate-only models predict the total disappearance of Araucaria's most suitable habitat by 2070, but incorporating topographic effects allows potential highland microrefugia to be identified. The legacy of 20th-century destruction is evident-more than a third of these likely holdouts have already lost their natural vegetation-and 21st-century climate change will leave just 3.5% of remnant forest and 28.4% of highland grasslands suitable for Araucaria. Existing protected areas cover only 2.5% of the surviving microrefugia for this culturally important species, and none occur in any designated indigenous territory. Our results suggest that anthropogenic climate change is likely to commit Araucaria to a second consecutive century of significant losses, but targeted interventions could help ensure its survival in the wild.

Muscle quality as a complementary prognostic tool in conjunction with sarcopenia assessment in younger and older individuals.

PURPOSE: This pilot study investigated differences in lean tissue mass, muscle strength, muscle quality (strength per unit of muscle mass; MQ), and functional performance in healthy younger and older individuals. The most robust predictors of appendicular lean mass (ALM) were then determined in each group. METHODS: Fifty younger (18-45 years) and 50 older (60-80 years) participants completed tests of upper and lower body strength alongside body composition by dual-energy X-ray absorptiometry from which upper- and lower-body MQ were estimated. Available cut-points for older people were used to determine low upper-body MQ in both groups. Low lower-body MQ was determined as at least two standard deviations below the mean of the younger group. Functional performance was assessed by gait speed. Sarcopenia was identified using two established definitions. RESULTS: Upper and lower body strength, ALM, lower-body MQ and gait speed were significantly higher in the younger group (all p < 0.002). Sarcopenia was identified in 2-4% of the older group. Low upper-body MQ was evident in 32% and 42% of the younger and older group, respectively. Low lower-body MQ was observed in 4% of younger participants, and 50% of older participants. In both groups, the most robust predictors of ALM were upper and lower body strength (young R2 = 0.74, 0.82; older R2 = 0.68, 0.72). CONCLUSIONS: Low MQ despite low prevalence rates of sarcopenia in both groups suggests a need for age-specific MQ cut-points. Muscle quality assessments might be useful complementary prognostic tools alongside existing sarcopenia definitions.

In It Together: A Qualitative Evaluation of Participant Experiences of a 10-Week, Group-Based, Workplace HIIT Program for Insufficiently Active Adults.

Using guidance from the reach, efficacy, adoption, implementation, and maintenance evaluation framework, we aimed to qualitatively evaluate the participant experiences of a workplace high-intensity interval training (HIIT) intervention. Twelve previously insufficiently active individuals (four males and eight females) were interviewed once as part of three focus groups. Perceptions of program satisfaction, barriers to and facilitators of adherence, and persistence to exercise were explored. HIIT initiates interest because of its novelty, provides a sense of accomplishment, and overcomes the barriers of perceived lack of time. The feeling of relatedness between the participants can attenuate negative unpleasant responses during the HIIT sessions. HIIT, in this workplace setting, is an acceptable intervention for physically inactive adults. However, participants were reluctant to maintain the same mode of exercise, believing that HIIT sessions were for the very fit.

Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults.

Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on immune function in sedentary adults. Twenty-seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function.

Immunofluorescence microscopy of SNAP23 in human skeletal muscle reveals colocalization with plasma membrane, lipid droplets, and mitochondria.

Synaptosomal-associated protein 23 (SNAP23) is a SNARE protein expressed abundantly in human skeletal muscle. Its established role is to mediate insulin-stimulated docking and fusion of glucose transporter 4 (GLUT4) with the plasma membrane. Recent in vitro research has proposed that SNAP23 may also play a role in the fusion of growing lipid droplets (LDs) and the channeling of LD-derived fatty acids (FAs) into neighboring mitochondria for ß-oxidation. This study investigates the subcellular distribution of SNAP23 in human skeletal muscle using immunofluorescence microscopy to confirm that SNAP23 localization supports the three proposed metabolic roles. Percutaneous biopsies were obtained from the m. vastus lateralis of six lean, healthy males in the rested, overnight fasted state. Cryosections were stained with antibodies targeting SNAP23, the mitochondrial marker cytochrome c oxidase and the plasma membrane marker dystrophin, whereas intramuscular LDs were stained using the neutral lipid dye oil red O. SNAP23 displayed areas of intense punctate staining in the intracellular regions of all muscle fibers and continuous intense staining in peripheral regions of the cell. Quantitation of confocal microscopy images showed colocalization of SNAP23 with the plasma membrane marker dystrophin (Pearson's correlation coefficient r = 0.50 ± 0.01). The intense punctate intracellular staining colocalized primarily with the mitochondrial marker cytochrome C oxidase (r = 0.50 ± 0.012) and to a lesser extent with LDs (r = 0.21 ± 0.01) visualized with oil red O. We conclude that the observed subcellular distribution of SNAP23 in human skeletal muscle supports the three aforementioned metabolic roles.

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health.

BACKGROUND: Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. PURPOSE: To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. METHODS: Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15-60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1). MICT participants performed continuous cycling (~70% HRmax, 30-45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. RESULTS: Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. CONCLUSIONS: HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity.

Visualization and quantitation of GLUT4 translocation in human skeletal muscle following glucose ingestion and exercise.

Insulin- and contraction-stimulated increases in glucose uptake into skeletal muscle occur in part as a result of the translocation of glucose transporter 4 (GLUT4) from intracellular stores to the plasma membrane (PM). This study aimed to use immunofluorescence microscopy in human skeletal muscle to quantify GLUT4 redistribution from intracellular stores to the PM in response to glucose feeding and exercise. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of ten insulin-sensitive men in the basal state and following 30 min of cycling exercise (65% VO2 max). Muscle biopsy samples were also taken from a second cohort of ten age-, BMI- and VO2 max-matched insulin-sensitive men in the basal state and 30 and 60 min following glucose feeding (75 g glucose). GLUT4 and dystrophin colocalization, measured using the Pearson's correlation coefficient, was increased following 30 min of cycling exercise (baseline r = 0.47 ± 0.01; post exercise r = 0.58 ± 0.02; P < 0.001) and 30 min after glucose ingestion (baseline r = 0.42 ± 0.02; 30 min r = 0.46 ± 0.02; P < 0.05). Large and small GLUT4 clusters were partially depleted following 30 min cycling exercise, but not 30 min after glucose feeding. This study has, for the first time, used immunofluorescence microscopy in human skeletal muscle to quantify increases in GLUT4 and dystrophin colocalization and depletion of GLUT4 from large and smaller clusters as evidence of net GLUT4 translocation to the PM.

Paxillin and focal adhesion kinase colocalise in human skeletal muscle and its associated microvasculature.

Focal adhesion kinase (FAK) and paxillin are functionally linked hormonal- and mechano-sensitive proteins. We aimed to describe paxillin's subcellular distribution using widefield and confocal immunofluorescence microscopy and test the hypothesis that FAK and paxillin colocalise in human skeletal muscle and its associated microvasculature. Percutaneous muscle biopsies were collected from the m. vastus lateralis of seven healthy males, and 5-µm cryosections were stained with anti-paxillin co-incubated with anti-dystrophin to identify the sarcolemma, anti-myosin heavy chain type I for fibre-type differentiation, anti-dihydropyridine receptor to identify T-tubules, lectin UEA-I to identify the endothelium of microvessels and anti-α-smooth muscle actin to identify vascular smooth muscle cells (VSMC). Colocalisation of anti-paxillin with anti-dystrophin or anti-FAK was quantified using Pearson's correlation coefficient on confocal microscopy images. Paxillin was primarily present in (sub)sarcolemmal regions of skeletal muscle fibres where it colocalised with dystrophin (r = 0.414 ± 0.026). The (sub)sarcolemmal paxillin immunofluorescence intensity was ~2.4-fold higher than in sarcoplasmic regions (P < 0.001) with sarcoplasmic paxillin immunofluorescence intensity ~10 % higher in type I than in type II fibres (P < 0.01). In some longitudinally orientated fibres, paxillin formed striations that corresponded to the I-band region. Paxillin immunostaining was highest in endothelial and VSMC and distributed heterogeneously in both cell types. FAK and paxillin colocalised at (sub)sarcolemmal regions and within the microvasculature (r = 0.367 ± 0.036). The first images of paxillin in human skeletal muscle suggest paxillin is present in (sub)sarcolemmal and I-band regions of muscle fibres and within the microvascular endothelium and VSMC. Colocalisation of FAK and paxillin supports their suggested role in hormonal and mechano-sensitive signalling.