Fibro-adipogenic progenitors in physiological adipogenesis and intermuscular adipose tissue remodeling.

Excessive accumulation of intermuscular adipose tissue (IMAT) is a common pathological feature in various metabolic and health conditions and can cause muscle atrophy, reduced function, inflammation, insulin resistance, cardiovascular issues, and unhealthy aging. Although IMAT results from fat accumulation in muscle, the mechanisms underlying its onset, development, cellular components, and functions remain unclear. IMAT levels are influenced by several factors, such as changes in the tissue environment, muscle type and origin, extent and duration of trauma, and persistent activation of fibro-adipogenic progenitors (FAPs). FAPs are a diverse and transcriptionally heterogeneous population of stromal cells essential for tissue maintenance, neuromuscular stability, and tissue regeneration. However, in cases of chronic inflammation and pathological conditions, FAPs expand and differentiate into adipocytes, resulting in the development of abnormal and ectopic IMAT. This review discusses the role of FAPs in adipogenesis and how they remodel IMAT. It highlights evidence supporting FAPs and FAP-derived adipocytes as constituents of IMAT, emphasizing their significance in adipose tissue maintenance and development, as well as their involvement in metabolic disorders, chronic pathologies and diseases. We also investigated the intricate molecular pathways and cell interactions governing FAP behavior, adipogenesis, and IMAT accumulation in chronic diseases and muscle deconditioning. Finally, we hypothesize that impaired cellular metabolic flexibility in dysfunctional muscles impacts FAPs, leading to IMAT. A deeper understanding of the biology of IMAT accumulation and the mechanisms regulating FAP behavior and fate are essential for the development of new therapeutic strategies for several debilitating conditions.

Next steps to advance general physical activity recommendations towards physical exercise prescription: a narrative review.

Physical inactivity is a major health concern, associated with the development of several non-communicable diseases and with an increased mortality rate. Therefore, promoting active lifestyles has become a crucial public health necessity for enhancing overall health and quality of life. The WHO guidelines for physical activity (PA) present valuable contributions in this respect; however, we believe that greater specificity should be added or complemented towards physical exercise (PE) testing, prescription and programming in future recommendations. In this review article, we suggest simple and practical tools accessible to the entire population to improve the specificity of this approach, highlighting aspects of PE programming used by trained subjects. By adopting these suggestions, exercise professionals, clinicians and physical trainers can optimise the current general PA recommendations towards PE prescription to improve fitness status and encourage PE adherence in the general population.

The Role of Omega-3 Polyunsaturated Fatty Acids and Their Lipid Mediators on Skeletal Muscle Regeneration: A Narrative Review.

Skeletal muscle is the largest tissue in the human body, comprising approximately 40% of body mass. After damage or injury, a healthy skeletal muscle is often fully regenerated; however, with aging and chronic diseases, the regeneration process is usually incomplete, resulting in the formation of fibrotic tissue, infiltration of intermuscular adipose tissue, and loss of muscle mass and strength, leading to a reduction in functional performance and quality of life. Accumulating evidence has shown that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and their lipid mediators (i.e., oxylipins and endocannabinoids) have the potential to enhance muscle regeneration by positively modulating the local and systemic inflammatory response to muscle injury. This review explores the process of muscle regeneration and how it is affected by acute and chronic inflammatory conditions, focusing on the potential role of n-3 PUFAs and their derivatives as positive modulators of skeletal muscle healing and regeneration.

A Short-Term Eccentric HIIT Induced Greater Reduction in Cardio-Metabolic Risk Markers in Comparison With Concentric HIIT in Sedentary Overweight Men.

Background: Steady-state eccentric exercise training improves cardiometabolic risk (CMR) despite lesser cardiovascular demands compared with load-matched concentric training. Whether a high-intensity interval eccentric training is also effective reducing CMR is unknown. Aim: To compare the effects of a short-term high-intensity interval eccentric training (ECC-HIIT) with high-intensity interval concentric training (CONC-HIIT) on CMR in sedentary overweight men. Methods: Twenty men (age: 27.9 ± 5.3y, body massindex: 29.1 ± 3.1 kg·m-2) were randomly assigned to ECC-HIIT (n = 10) or CONC-HIIT (n = 10) delivered as six sessions, including 4 x 5:2 min work-to-rest ratio, at 80% peak concentric power output. Heart rate (HR), rate of perceived exertion (RPE) and muscle soreness weremonitored during training sessions. Training effects on lipid profile, insulin sensitivity (HOMA-IR), body composition, thigh circumference, isometric knee extensors maximal strength, resting systolic and diastolic blood pressure (SBP and DBP) were determined. Results: Average training HR and RPE were -29%and -50%lower in ECC-HIIT in comparison with CONC-HIIT. Muscle soreness was initially greater after ECC-HIIT compared with CONC-HIIT. Significant changes in total and low-density lipoprotein cholesterol (-7.0 ± 8.7%; p = .02 and -6.3 ± 14.4%; p = .03), SBP (-9.8 ± 7.8%; p = .002), and maximal thigh circumference (+2.5 ± 3.1%; p = .02) were observed following ECC-HIIT. No changes in any CMR marker were observed after CONC-HIIT. Moderate-to-large training effect sizes were obtained in thigh circumference, SBP, total cholesterol and low-density lipoprotein cholesterol in response to ECC-HIIT. Conclusion: A two-week ECC-HIIT was well-tolerated and induced rapid onset improvements in cholesterol and blood pressure compared to conventional CONC-HIIT in sedentary overweight men.

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.

Effects of eccentric, concentric and eccentric/concentric training on muscle function and mass, functional performance, cardiometabolic health, quality of life and molecular adaptations of skeletal muscle in COPD patients: a multicentre randomised trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third cause of death worldwide. COPD is characterised by dyspnoea, limited exercise tolerance, and muscle dysfunction. Muscle dysfunction has been linked to dysregulation between muscle protein synthesis, myogenesis and degradation mechanisms. Conventional concentric cycling has been shown to improve several clinical outcomes and reduce muscle wasting in COPD patients. Eccentric cycling is a less explored exercise modality that allows higher training workloads imposing lower cardio-metabolic demand during exercise, which has shown to induce greater muscle mass and strength gains after training. Interestingly, the combination of eccentric and concentric cycling training has scarcely been explored. The molecular adaptations of skeletal muscle after exercise interventions in COPD have shown equivocal results. The mechanisms of muscle wasting in COPD and whether it can be reversed by exercise training are unclear. Therefore, this study aims two-fold: (1) to compare the effects of 12 weeks of eccentric (ECC), concentric (CONC), and combined eccentric/concentric (ECC/CONC) cycling training on muscle mass and function, cardiometabolic health, physical activity levels and quality of life in severe COPD patients; and (2) to examine the molecular adaptations regulating muscle growth after training, and whether they occur similarly in specific muscle fibres (i.e., I, IIa and IIx). METHODS: Study 1 will compare the effects of 12 weeks of CONC, ECC, versus ECC/CONC training on muscle mass and function, cardiometabolic health, levels of physical activity and quality of life of severe COPD patients using a multicentre randomised trial. Study 2 will investigate the effects of these training modalities on the molecular adaptations regulating muscle protein synthesis, myogenesis and muscle degradation in a subgroup of patients from Study 1. Changes in muscle fibres morphology, protein content, genes, and microRNA expression involved in skeletal muscle growth will be analysed in specific fibre-type pools. DISCUSSION: We aim to demonstrate that a combination of eccentric and concentric exercise could maximise the improvements in clinical outcomes and may be ideal for COPD patients. We also expect to unravel the molecular mechanisms underpinning muscle mass regulation after training in severe COPD patients. TRIAL REGISTRY: Deutshches Register Klinischer Studien; Trial registration: DRKS00027331; Date of registration: 12 January 2022. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027331 .

Reproducibility of Maximum Respiratory Pressure Assessment: A Systematic Review and Meta-analysis.

BACKGROUND: Accurate assessment of maximum respiratory pressure is vital when tracking disease progression and devising treatment strategies. Previous studies indicate a learning effect when undertaking maximum respiratory pressure measurements. The extent of this learning effect and methodologies undertaken to mitigate this learning effect have not been investigated systematically. RESEARCH QUESTION: What is the magnitude of improvements in maximum respiratory pressure in response to respiratory muscle warm-up protocols and repeated measures of maximum respiratory pressure in healthy individuals and clinical populations? METHODS: A comprehensive search of electronic databases was undertaken during August 2021 for studies examining the intrarater reliability of maximum inspiratory or expiratory pressure, or both, studies developing a protocol or an intervention to obtain maximum values, and studies analyzing the reliability of repeated maneuvers in a single testing session in healthy individuals and clinical populations. Included articles were analyzed critically using two appraisal tools. Standardized mean differences with 95% CIs were calculated and corrected for the sample size as a measure of the magnitude of change in maximum respiratory pressure outcomes. RESULTS: Of the 1,969 articles retrieved, 32 were included in the meta-analysis. Eighteen studies included healthy individuals and 14 studies included individuals with chronic medical conditions. The overall effect of inspiratory muscle warm-up protocols was higher (effects size [ES], 0.40; 95% CI, 0.17-0.63) in comparison with single testing session studies (ES, 0.20; 95% CI, 0.05-0.35) and studies performing repeated testing sessions of maximum respiratory pressure (ES, 0.14; 95% CI, 0.07-022). INTERPRETATION: Inspiratory muscles warm-up procedures induce higher increases in maximum inspiratory pressure in comparison with single and repeated testing sessions of maximum respiratory pressure in healthy individuals. Warm-up protocols are more effective to obtain the maximum performance of inspiratory muscles in one testing session in comparison with other methods. TRIAL REGISTRY: PROSPERO; No.: CRD42022304591; URL: https://www.crd.york.ac.uk/prospero/.

Similar Adaptations to 10 Weeks Concurrent Training on Metabolic Markers and Physical Performance in Young, Adult, and Older Adult Women.

It has been proposed that the combination of high-intensity aerobic exercises and resistance training (RT) known as concurrent training (CT) could improve metabolic syndrome (MetS) markers, and that the exercise mixture in CT could dampen muscle anaerobic pathways, a result known as the interference effect. However, there is scarce evidence on its effects in women across different ages. Therefore, we sought to determine the effects of a 10-week CT intervention on MetS markers and endurance performance in adult women and compared age-related differences between young, adult, and older participants. A total of 112 women with >1 MetS risk factors were included in the study. Participants were allocated to different groups according to the following cutoff age ranges: 20-29years (y), n = 25; 30-39y, n = 35; 40-49y, n = 43; and 50-59y, n = 53. Participants performed 10 weeks of CT, including resistance training (RT), involving six major muscle groups, and high-intensity interval training (HIIT) in a cycle ergometer. Anthropometric, cardiovascular, metabolic, and performance outcomes were assessed before and after the intervention. The CT induced significant improvements in waist circumference (WC) (20-29y: -2.5; 30-39y: -4.1; 40-49y: -4.2; 50-59y: -2.8 Δcm) and the distance achieved in the six-minute walking test (6Mwt) (20-29y: +47.6; 30-39y: +66.0; 40-49y: +43.0; 50-59y: +58.6 Δm) across all age groups, without significant differences between groups. In addition, a significant correlation was found between 6Mwt and WC, independent of age. In conclusion, our results showed that a 10-week CT intervention improved MetS risk factors in women, suggesting that the beneficial effects promoted by CT are independent of age and confirming CT as an effective, age-independent training regimen to improve metabolic health in women.

Exercise Training to Decrease Ectopic Intermuscular Adipose Tissue in Individuals With Chronic Diseases: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to evaluate the effect of exercise training on ectopic fat within skeletal muscle (intermuscular adipose tissue [IMAT]) in adult populations with chronic diseases. METHODS: A literature search was conducted in relevant databases to identify randomized controlled trials (RCTs) from inception. Selected studies examined the effect of aerobic training (AET), resistance training (RT), or combined training (COM) on IMAT as assessed by noninvasive magnetic resonance imagery or computed tomography. Eligibility was determined using Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data extraction was performed using the population (P), intervention (I), comparison (C), outcome (O), timing (T), and settings (S) approach. Methodological quality was analyzed by the Cochrane risk of bias assessment. Standardized effect sizes (ES) with 95% CIs were calculated. Heterogeneity among studies was quantified using I2 statistics. Subgroup and meta-regression analyses were included. Risk of publication bias was examined by the Egger regression test. RESULTS: Nineteen RCTs included 962 adults (628 women; age range = 34.8-93.4 years) with different chronic conditions that participated in 10 AET, 12 RT, and 5 COM interventions. The quality of studies was deemed moderate. Overall, the effect of exercise on IMAT was small (ES = 0.24; 95% CI = 0.10 to 0.37; heterogeneity I2 = 0.0%) compared with no exercise or control interventions. Moderate-intensity AET and COM had larger ES compared with RT regardless of intensity. This effect was associated with exercise-induced body weight and fat mass losses. Subgroup analysis revealed larger ES in studies assessing IMAT by magnetic resonance imagery compared with computed tomography in adults and middle-aged individuals compared with older adults and in participants who were HIV+ compared with other diagnoses. CONCLUSION: AET and COM of moderate intensity reduce IMAT in individuals from 18 to 65 years of age who are affected by chronic diseases. This effect is associated with exercise-induced body weight and fat mass losses. In older individuals who are frail and patients at an advanced disease stage, exercise may result in a paradoxical IMAT accumulation. IMPACT: In people affected by chronic conditions, IMAT accumulation induces muscle mass and strength losses, decline in physical performance, inflammation, and metabolic alterations. The present study shows that moderate-intensity AET or COM prevent or reduce IMAT in these conditions. Thus, the deleterious effect of IMAT on skeletal muscle homeostasis may be reverted by a properly prescribed exercise regime. The findings of the present systematic review are critical for physical therapists and health care professionals because they emphasize the therapeutic role of exercise and provide recommendations for exercise prescription that ultimately may have a positive impact on the course of disease, recovery of functionality, and independence. LAY SUMMARY: Aerobic exercise (eg, walking/jogging, cycling) alone or combined with resistance exercise (strength training with free-weights, kettle bells, or gym equipment) is effective in reducing fat streaks that infiltrate muscles and impair muscle function and growth, particularly in adults affected by chronic diseases.

Gender differences in blood pressure and body composition in schoolchildren ascendants from Amerindian and European.

Background: In spite of there are a wide knowledge of the prevalence of hypertension in adult, there is poor information on schoolchildren of different ethnicity and gender.Aim: To compare the levels of blood pressure and other cardiometabolic risk factors for hypertension between schoolchildren of different gender and ethnicity.Material and methods: In a cross-sectional study, 540 schoolchildren (6-13 years) ascendants from a Chilean public school population were analysed by ethnicity and gender in four groups (Mapuches N = 55; European boys N = 199, and Mapuches N = 64, and European girls N = 222). The study included the measurement of cardiovascular (systolic and diastolic blood pressure) as main outcomes, as well as other cardiovascular (resting heart rate), body composition (body mass, BMI, waist circumference, fat mass, muscle mass), muscle strength (handgrip strength of dominant, non-dominant, and mean handgrip strength) as additional cardiometabolic outcomes.Results: The systolic blood pressure was significantly higher in Mapuches girls 126 ± 4 vs. their European counterparts 119 ± 3 mmHg, P < .002, as well as diastolic blood pressure, was higher in Mapuches girls 82 ± 5 vs. European girls 74 ± 3 mmHg, P < .0001. There were more 'prehypertensive' Mapuches girls 10 (15.6%) vs. European peers 22 (9.9%) at P < .0001, and the 'hypertension' was significantly more prevalent in Mapuches boys 19 (34.5%) vs. European peers 39 (19.4%) at P < .0001, as well as in Mapuches girls 16 (25%) vs. European peers 33 (14.9%) at P < .0001. The 'obesity' was less prevalent in Mapuches 10 (18.2%) vs. European boys 55 (27.4%) at P < .0001. The waist circumference was high in European 74 ± 4 vs. Mapuches 67 ± 6 cm, P < .012 in boys, although, waist circumference was high in Mapuches girls 75 ± 5 vs. European peers 71 ± 3 cm, P < .021. There were higher levels of muscle mass in Mapuches boys 19.5 ± 12 vs. European peers 17.1 ± 4 kg, P < .0001.Conclusion: Mapuches girls show higher levels of systolic and diastolic BP than European girls, Mapuches boys and girls are more hypertensive than European peers, but are less obese than European schoolchildren peers. These cardiometabolic differences that are more detrimental for endemic ethnic Latinoamerican groups are in need to be explored further.

Exercise and GLUT4.

The glucose transporter GLUT4 is critical for skeletal muscle glucose uptake in response to insulin and muscle contraction/exercise. Exercise increases GLUT4 translocation to the sarcolemma and t-tubule and, over the longer term, total GLUT4 protein content. Here, we review key aspects of GLUT4 biology in relation to exercise, with a focus on exercise-induced GLUT4 translocation, postexercise metabolism and muscle insulin sensitivity, and exercise effects on GLUT4 expression.

Interplay between rotational work shift and high altitude-related chronic intermittent hypobaric hypoxia on cardiovascular health and sleep quality in Chilean miners.

Mining activities expose workers to diverse working conditions, rotational shifts and high altitude-related hypobaric hypoxia. Separately, each condition has been reported having a negative impact on miners' health risk; however, the combination of both stressors has been poorly explored. The present study aimed to analyse the effects of exposure to rotational work shift (RWS) alone or in combination with high altitude-related chronic intermittent hypobaric hypoxia (CIHH) on cardiometabolic, physical activity and sleep quality related markers in copper miners from Los Pelambres mine in Chile. One hundred and eleven male miners working in RWS with or without CIHH were included. Anthropometrics measures, sleep quality assessment, physical activity level (PAL) and handgrip strength were evaluated. Exposure to CIHH exacerbated the detrimental effects of RWS as miners exposed to the combination of RWS and CIHH where more obese and had a wider neck circumference, reduced PAL at work and worsened sleep quality. Practitioner summary: The purpose was to assess cardiometabolic health and sleep quality markers associated with the combined effects of rotational shift work and high altitude-related intermittent hypobaric hypoxia in miners. Findings showed a wider neck circumference, lower physical activity level and higher prevalence of poor sleep quality in exposed miners. Abbreviations: ANOVA: analysis of variance; BM: body mass; BMI: body mass index; CI: confidence intervals; CIHH: chronic intermittent hypobaric hypoxia; CV: cardiovascular; CVR: cardiovascular risk; HA: high altitude; HACE: high-altitude cerebral edema; HGS: handgrip strength; IPAQ-SF: International Physical Activity Questionnaire - Short Form; LSD: Fisher's least standardized difference; MANCOVA: multivariate general lineal model; MET: metabolic equivalent; PAL: physical activity level; PSQI: Pittsburg sleep quality index; RWS: rotational work shift; WHR: waist-to-hip ratio.

Defective fasting-induced PKA activation impairs adipose tissue glycogen degradation in obese Zucker rats.

BACKGROUND: Obesity is associated with development of insulin resistance in adipose tissue (AT). Human obesity has been associated with increased glycogen deposition in adipocytes. Adipocytes synthesise glycogen prior to the formation of lipids. The present study examined adipose glycogen content in obese Zucker rats and the effect of fasting on glycogen-metabolising enzymes. We hypothesised that obesity imposes a blunted response to fasting through impaired activation of glycogen-metabolizing enzymes, which dampens glycogen mobilization in obese Zucker rats. METHODS: We investigated the effect of 24h fasting on AT glycogen metabolism in 12-week old obese Zucker rats. Epididymal fat pads were collected from rats fed ad-libitum and fasted for 24h. Glycogen content, glycogen synthase and phosphorylase enzyme activity, and PKA activity were analysed as well as total and phosphorylated protein content for glycogen-metabolizing enzymes glycogen synthase and phosphorylase, glucose transporter GLUT4, and cAMP-dependent response element binding protein levels. RESULTS: Twelve-week old obese Zucker rats showed increased AT glycogen content (adipose glycogen content [mean ± SD], lean: 3.95 ± 2.78 to 0.75 + 0.69 µg.mg-1; p < 0.005 fed vs fasted, and obese: 5.23 ± 3.38 to 5.019 ± 1.99 µg.mg-1; p = ns fed and fasted and p < 0.005 lean vs obese), and impaired fasting-induced glycogen mobilization following a 24h fast. These defects were associated with dysfunctional glycogen-metabolizing enzymes, characterized by: (1) blunted phosphorylation-mediated activation and downregulated protein expression of glycogen phosphorylase, and (2) an impaired phosphorylation-mediated inactivation of glycogen synthase. Furthermore, these defects were related to impaired fasting-induced protein kinase A (PKA) activation. CONCLUSION: This study provides evidence of a defective glycogen metabolism in the adipose associated with impaired fasting-induced activation of the upstream kinase protein kinase A, which render a converging point to obesity-related primary alterations in carbohydrate and lipid metabolism in the AT.

Preventing metabolic syndrome in morbid obesity with resistance training: Reporting interindividual variability.

BACKGROUND AND AIMS: Resistant training (RT) improves health markers in obesity, but its effects in morbid obesity are unknown. We aimed to determine the effects of a RT-program in preventing/attenuating the metabolic syndrome (MetS) in patients with morbid obesity. A second aim was to report the interindividual variability in terms of improvements in MetS markers and other related co-variables. METHODS AND RESULTS: Twenty-one adults with obesity or morbid obesity were divided into two groups based on body mass index (BMI): a control obesity (CO, n = 7, BMI ≥35 < 40.0 kg/m2) and a morbid obese group (MO, n = 14, BMI ≥40 kg/m2). Participants completed a 20-week RT-program (3 sessions/week, 4-8 exercise) using free weights. Participants were assessed for MetS markers (waist circumference, systolic and diastolic blood pressure [BP], fasting glucose, high-density lipoproteins, and triglycerides) and other co-variables (total cholesterol, low-density lipoprotein, one-maximum repetition of biceps curl, and handgrip strength, 6 min walking test). Significant reductions in MetS markers were observed in both CO and MO groups (P < 0.05 to P < 0.0001), but significant reductions in diastolic BP and increases in HDL-C were noted only in the MO group (P < 0.0001). Changes in waist circumference, and systolic and diastolic BP were significantly greater only in the MO group (P < 0.001), but the CO group presented a greater fasting glucose decreases (P < 0.0001). The prevalence of non-responders between CO and MO groups was similar in the MetS outcomes. CONCLUSIONS: RT promotes greater improvements in overall MetS outcomes waist circumference, BP, and plasma triglycerides in patients with morbid obesity than in obese peers, with no overall differences in the prevalence of non-responders. CLINICAL TRIAL NUMBER: NCT03921853 at www.clinicaltrials.gov.

Exercise serum increases GLUT4 in human adipocytes.

NEW FINDINGS: What is the central question of this study? Do circulating factors mediate exercise-induced effects on adipose tissue GLUT4 expression? What is the main finding and its importance? Serum (10%) obtained from human volunteers immediately after a single exercise bout increased GLUT4 protein levels in human adipocytes in culture. This result suggests that circulating factors might mediate the effects of exercise on adipose tissue GLUT4 and prompts further effort to identify the specific factor(s) and tissue(s) of origin. ABSTRACT: In this study, we tested the hypothesis that circulating factors generated during exercise increase adipose tissue GLUT4 expression. Serum was obtained from eight healthy subjects before and after 60 min of cycling exercise, and primary adipocytes were cultured from stromal vascular fractions that were isolated from subcutaneous abdominal adipose tissue samples from one healthy, male volunteer. A 48 h exposure of human primary adipocytes to 10% serum obtained after exercise increased GLUT4 protein expression, on average, by 12% compared with exposure to 10% serum obtained at rest, before exercise. GLUT4 mRNA levels were increased after 12 h of exposure to exercise serum but were unchanged after 6 and 24 h of exposure. Our results suggest that circulating factors might mediate the effects of exercise on adipose tissue GLUT4 expression and encourage further efforts to identify the potential factor(s), tissue(s) of origin and physiological relevance.

Exercise and GLUT4 in human subcutaneous adipose tissue.

To examine the effect of acute and chronic exercise on adipose tissue GLUT4 expression, a total of 20 healthy, male subjects performed one of two studies. Ten subjects performed cycle ergometer exercise for 60 min at 73 ± 2% VO2 peak and abdominal adipose tissue samples were obtained immediately before and after exercise and after 3 h of recovery. Another 10 subjects completed 10 days of exercise training, comprising a combination of six sessions of 60 min at 75% VO2 peak and four sessions of 6 × 5 min at 90% VO2 peak, separated by 3 min at 40% VO2 peak. Abdominal adipose tissue and vastus lateralis muscle samples were obtained before training and 24 h after the last training session. A single bout of exercise did not change adipose tissue GLUT4 mRNA; however, there was a small, but significant, reduction in adipose tissue GLUT4 protein expression 3 h after exercise. There were no changes in adipose tissue GLUT4 or COX-IV expression following exercise training. In contrast, skeletal muscle GLUT4 and COX-IV were increased by 47% and 44%, respectively following exercise training. The exercise training-induced increase in GLUT4 expression was similar in both type I and type IIa single muscle fibers. Our results indicate that neither a single exercise bout, nor 10 days of exercise training, increased adipose tissue GLUT4, in contrast with the increases observed in skeletal muscle GLUT4 expression.

No evidence of direct association between GLUT4 and glycogen in human skeletal muscle.

Previous studies have demonstrated that exercise increases whole body and skeletal muscle insulin sensitivity that is linked with increased GLUT4 at the plasma membrane following insulin stimulation and associated with muscle glycogen depletion. To assess the potential direct association between muscle glycogen and GLUT4, seven untrained, male subjects exercised for 60 min at ~75% VO2 peak, with muscle samples obtained by percutaneous needle biopsy immediately before and after exercise. Exercise reduced muscle glycogen content by ~43%. An ultracentrifugation protocol resulted in a ~2-3-fold enriched glycogen fraction from muscle samples for analysis. Total GLUT4 content was unaltered by exercise and we were unable to detect any GLUT4 in glycogen fractions, either with or without amylase treatment. In skinned muscle fiber segments, there was very little, if any, GLUT4 detected in wash solutions, except following exposure to 1% Triton X-100. Amylase treatment of single fibers did not increase GLUT4 in the wash solution and there were no differences in GLUT4 content between fibers obtained before or after exercise for any of the wash treatments. Our results indicate no direct association between GLUT4 and glycogen in human skeletal muscle, before or after exercise, and suggest that alterations in GLUT4 translocation associated with exercise-induced muscle glycogen depletion are mediated via other mechanisms.

Changes in the heart rate recovery to endurance effort after high intensity interval, strength, and concurrent exercise training in patients with insulin resistance.

BACKGROUND: The aim of this study was to assess the effects of three exercise training programs in the adaptation of the heart rate recovery of patients with insulin resistance. METHODS: We studied 43 women with insulin resistance, which were assigned to three training groups: 1) high intensity interval training (HIT, age 39.0±10 years); 2) strength training (ST, age 33.9±9.4 years); 3) HIT+ST (MIXT, age 43.3±8.1 years); and 4) control group (CG, age 40.1±11 years). Heart rate was measured at rest (HRrest), during the 2-km-walking-test (UKKT) for mean (HRDE), and maximum (HRMDE) values, and during the recovery at one, two, and three minutes after the UKKT. Additionally, anthropometric measurements (body mass and body mass index) were assessed. RESULTS: HIT significantly decreased HRrest and HRDE (-4.5% and -2% respectively, P<0.05). MIXT training also decreased HRDE in -3% whilst both average and maximal HR during UKK were significantly increased in the control group HRDE (+2% and +3% respectively). Moreover, there were significant reductions in HR recovery at 1, 2 and 3 minutes after both HIT and MIXT training, whereas these values were increased in control group. CONCLUSIONS: Our findings suggest that HIT induces meaningful cardiovascular adaptations in patient with insulin resistance, reducing heart rate at rest, as well as during and after exercise, and that complementary strength training increases these adaptations.

The 3T3-L1 adipocyte glycogen proteome.

BACKGROUND: Glycogen is a branched polysaccharide of glucose residues, consisting of α-1-4 glycosidic linkages with α-1-6 branches that together form multi-layered particles ranging in size from 30 nm to 300 nm. Glycogen spatial conformation and intracellular organization are highly regulated processes. Glycogen particles interact with their metabolizing enzymes and are associated with a variety of proteins that intervene in its biology, controlling its structure, particle size and sub-cellular distribution. The function of glycogen in adipose tissue is not well understood but appears to have a pivotal role as a regulatory mechanism informing the cells on substrate availability for triacylglycerol synthesis. To provide new molecular insights into the role of adipocyte glycogen we analyzed the glycogen-associated proteome from differentiated 3T3-L1-adipocytes. RESULTS: Glycogen particles from 3T3-L1-adipocytes were purified using a series of centrifugation steps followed by specific elution of glycogen bound proteins using α-1,4 glucose oligosaccharides, or maltodextrins, and tandem mass spectrometry. We identified regulatory proteins, 14-3-3 proteins, RACK1 and protein phosphatase 1 glycogen targeting subunit 3D. Evidence was also obtained for a regulated subcellular distribution of the glycogen particle: metabolic and mitochondrial proteins were abundant. Unlike the recently analyzed hepatic glycogen proteome, no endoplasmic proteins were detected, along with the recently described starch-binding domain protein 1. Other regulatory proteins which have previously been described as glycogen-associated proteins were not detected, including laforin, the AMPK beta-subunit and protein targeting to glycogen (PTG). CONCLUSIONS: These data provide new molecular insights into the regulation of glycogen-bound proteins that are associated with the maintenance, organization and localization of the adipocyte glycogen particle.