Beyond muscles: Investigating immunoregulatory myokines in acute resistance exercise - A systematic review and meta-analysis.

Myokines, released from the muscle, enable communication between the working muscles and other tissues. Their release during physical exercise is assumed to depend on immune-hormonal-metabolic interactions concerning mode (endurance or resistance exercise), duration, and intensity. This meta-analysis aims to examine the acute changes of circulating myokines inducing immunoregulatory effects caused by a bout of resistance exercise and to consider potential moderators of the results. Based on this selection strategy, a systematic literature search was conducted for resistance exercise intervention studies measuring interleukin (IL-) 6, IL-10, IL-1ra, tumor necrosis factor (TNF-) α, IL-15, IL-7, transforming growth factor (TGF-) ß1, and fractalkines (FKN) before and immediately after resistance exercise in healthy individuals. Random-effects meta-analysis was performed for each myokine. We identified a moderate positive effect of resistance exercise for IL-6 and IL-1ra. Regarding IL-15 and TNF-α, small to moderate effects were found. For IL-10, no significant effect was observed. Due to no data, meta-analyses for IL-7, TGF-ß1, and FKN could not be performed. No moderators (training status, type of exercise, risk of bias, age, sex, time of day, exercise volume, exercise intensity, exercise dose) of the results were detected for all tested myokines. Taken together, this systematic review and meta-analysis showed immediate positive effects of an acute resistance exercise session on IL-6, IL-1ra, TNF-α, and IL-15 levels.

Nuclear-localized androgen receptor content following resistance exercise training is associated with hypertrophy in males but not females.

Androgen receptor (AR) content has been implicated in the differential response between high and low responders following resistance exercise training (RET). However, the influence of AR expression on acute skeletal muscle damage and whether it may influence the adaptive response to RET in females is poorly understood. Thus, the purpose of this exploratory examination was to 1) investigate changes in AR content during skeletal muscle repair and 2) characterize AR-mediated sex-based differences following RET. A skeletal muscle biopsy from the vastus lateralis was obtained from 26 healthy young men (n = 13) and women (n = 13) at baseline and following 300 eccentric kicks. Subsequently, participants performed 10 weeks of full-body RET and a final muscle biopsy was collected. In the untrained state, AR mRNA expression was associated with paired box protein-7 (PAX7) mRNA in males. For the first time in human skeletal muscle, we quantified AR content in the myofiber and localized to the nucleus where AR has been shown to trigger cellular outcomes related to growth. Upon eccentric damage, nuclear-associated AR (nAR) content increased (p < .05) in males and not females. Males with the greatest increase in cross-sectional area (CSA) post-RET had more (p < .05) nAR content than females with the greatest gain CSA. Collectively, skeletal muscle damage and RET increased AR protein, and both gene and hypertrophy measures revealed sex differences in relation to AR. These findings suggest that AR content but more importantly, nuclear localization, is a factor that differentiates RET-induced hypertrophy between males and females.

Comparative effects of 8-week combined resistance exercise training and alternate-day calorie restriction on soluble epidermal growth factor receptor (sEGFR) and adipsin in obese men.

This study investigated the combined effects of resistance exercise training (RET) and alternate-day calorie restriction (ADCR) on body composition, insulin resistance (IR), insulin resistance-related biomarkers (adipokine adipsin and hepatokine soluble EFGR), and weight loss in obese men. The findings revealed that RET + ADCR induced the greatest reductions in body weight, body fat percentage, and waist-to-hip ratio (WHR) compared to RET and ADCR alone (p < 0.05). Additionally, RET + ADCR resulted in the most significant improvements in IR, as measured by HOMA-IR, and in circulating levels of adipsin and soluble EFGR (p < 0.05). These findings suggest that combining RET and ADCR may be a more effective strategy for improving metabolic health, including body composition, IR, and metabolic tissues' functions, in obese men than either intervention alone.

Exercise in Octogenarians: How Much Is Too Little?

The global population is rapidly aging, with predictions of many more people living beyond 85 years. Age-related physiological adaptations predispose to decrements in physical function and functional capacity, the rate of which can be accelerated by chronic disease and prolonged physical inactivity. Decrements in physical function exacerbate the risk of chronic disease, disability, dependency, and frailty with advancing age. Regular exercise positively influences health status, physical function, and disease risk in adults of all ages. Herein, we review the role of structured exercise training in the oldest old on cardiorespiratory fitness and muscular strength and power, attributes critical for physical function, mobility, and independent living.

Resistance exercise lowers blood pressure and improves vascular endothelial function in individuals with elevated blood pressure or stage-1 hypertension.

Lifestyle modifications are the first-line treatment recommendation for elevated blood pressure (BP) or stage-1 hypertension (E/S1H) and include resistance exercise training (RET). The purpose of the current study was to examine the effect of a 9-wk RET intervention in line with the current exercise guidelines for individuals with E/S1H on resting peripheral and central BP, vascular endothelial function, central arterial stiffness, autonomic function, and inflammation in middle-aged and older adults (MA/O) with untreated E/S1H. Twenty-six MA/O adults (54 ± 6 yr; 16 females/10 males) with E/S1H engaged in either 9 wk of 3 days/wk RET (n = 13) or a nonexercise control (Con; n = 13). Pre- and postintervention measures included peripheral and central systolic (SBP and cSBP) and diastolic BP (DBP and cDBP), flow-mediated dilation (FMD), carotid-femoral pulse wave velocity (cfPWV), cardiovagal baroreflex sensitivity (BRS), cardiac output (CO), total peripheral resistance (TPR), heart rate variability (HRV), and C-reactive protein (CRP). RET caused significant reductions in SBP {mean change ± 95% CI = [-7.9 (-12.1, -3.6) mmHg; P < 0.001]}, cSBP [6.8 (-10.8, -2.7) mmHg; P < 0.001)], DBP [4.8 (-10.3, -1.2) mmHg; P < 0.001], and cDBP [-5.1 (-8.9, -1.3) mmHg; P < 0.001]; increases in FMD [+2.37 (0.61, 4.14)%; P = 0.004] and CO [+1.21 (0.26, 2.15) L/min; P = 0.006]; and a reduction in TPR [-398 (-778, -19) mmHg·s/L; P = 0.028]. RET had no effect on cfPWV, BRS, HRV, or CRP relative to Con (P ≥ 0.20). These data suggest that RET reduces BP in MA/O adults with E/S1H alongside increased peripheral vascular function and decreased TPR without affecting cardiovagal function or central arterial stiffness.NEW & NOTEWORTHY This is among the first studies to investigate the effects of chronic resistance exercise training on blood pressure (BP) and putative BP regulating mechanisms in middle-aged and older adults with untreated elevated BP or stage-1 hypertension in a randomized, nonexercise-controlled trial. Nine weeks of resistance exercise training elicits 4- to 8-mmHg improvements in systolic and diastolic BP alongside improvements in vascular endothelial function and total peripheral resistance without influencing central arterial stiffness or cardiovagal function.

Cerebrovascular adaptations to habitual resistance exercise with aging.

Resistance training (RT) is associated with improved metabolism, bone density, muscular strength, and lower risk of osteoporosis, sarcopenia, and cardiovascular disease. Although RT imparts many physiological benefits, cerebrovascular adaptations to chronic RT are not well defined. Participation in RT is associated with greater resting peripheral arterial diameters, improved endothelial function, and general cardiovascular health, whereas simultaneously linked to reductions in central arterial compliance. Rapid blood pressure fluctuations during resistance exercise, combined with reduced arterial compliance, could lead to cerebral microvasculature damage and subsequent cerebral hypoperfusion. Reductions in cerebral blood flow (CBF) accompany normal aging, where chronic reductions in CBF are associated with changes in brain structure and function, and increased risk of neurodegeneration. It remains unclear whether reductions in arterial compliance with RT relate to subclinical cerebrovascular pathology, or if such adaptations require interpretation in the context of RT specifically. The purpose of this narrative review is to synthesize literature pertaining to cerebrovascular adaptations to RT at different stages of the life span. This review also aims to identify gaps in the current understanding of the long-term impacts of RT on cerebral hemodynamics and provide a mechanistic rationale for these adaptations as they relate to aging, cerebral vasculature, and overall brain health.

Integrating analysis of mRNA expression profiles indicates Sgk1 as a key mediator in muscle-brain crosstalk during resistance exercise.

Abundant evidence has shown the protective effect of aerobic exercise on central neuronal system, however, research about resistance exercise remains limited. To evaluate the effect and potential molecular mechanisms of resistance exercise in improving cognition and mental health, three-month-old male C57BL/6J mice underwent resistance training for five weeks. Body parameters, cognitive performance and synaptic plasticity were then assessed. In both groups, total RNA from the frontal cortex, hippocampus and gastrocnemius was isolated and sequenced, GO term and KEGG analysis were performed to identify molecular mechanisms. The results from RNA sequencing were then verified by RT-PCR. Our data found that mice in training group showed reduced anxiety-like behavior and better spatial memory. Accordingly, resistance exercise specifically increased the number of thin spines without affecting the number of other kind of spines. mRNA sequence analysis showed that resistance exercise induced differential expression of hundreds of genes in the above three tissues. KEGG analysis indicated the FoxO signaling pathway the most significant changed pathway throughout the brain and muscle. GO terms analysis showed that Sgk1 was enriched in the three key cognition related BP, including long-term memory, learning or memory and memory, and the expression level of Sgk1 was positive related with cognitive performance in the water maze. In conclusion, resistance exercise improved the mental health, cognition and synaptic plasticity of mice. Integrating analysis of mRNA expression profiles in frontal cortex, hippocampus and muscle reveals Sgk1 as the key mediator in brain-muscle crosstalk.

Revisiting the roles of glucose transporters in skeletal muscle physiology: is GLUT10 a novel player?

Skeletal muscle is the largest metabolic tissue responsible for systemic glucose handling. Glucose uptake into skeletal tissue is highly dynamic and delicately regulated, in part through the controlled expression and subcellular trafficking of multiple types of glucose transporters. Although the roles of GLUT4 in skeletal muscle metabolism are well established, the physiological significance of other, seemingly redundant, glucose transporters remain incompletely understood. Nonetheless, recent studies have shed light on the roles of several glucose transporters, such as GLUT1 and GLUT10, in skeletal muscle. Mice experiments suggest that GLUT10 could be a novel player in skeletal muscle metabolism in the context of mechanical overload, which is in line with the meta-analytical results of gene expression changes after resistance exercise in humans. Herein we discuss the knowns, unknowns, and implications of these recent findings.

BE-WEL trial (breast: evaluation of weight and exercise for lymphoedema) testing weight control and exercise programmes for women with breast cancer related lymphoedema: a feasibility trial.

PURPOSE: A combined body weight loss and upper body/arm exercise programme is a potential strategy for managing Breast cancer related lymphoedema (BCRL), but there is limited data on the best method for delivery or its potential efficacy. METHODS: Fifty-seven women with overweight/obesity and BCRL were randomised to a 12 week supervised (n = 12) or home-based combined weight loss and upper body/arm exercise programme (n = 16), a home-based upper-body arm exercise only programme (n = 17) or standard care (n = 12). Primary outcomes were uptake, retention and changes in weight and change in Relative Arm Volume Increase (RAVI) using analysis of covariance (ANCOVA). RESULTS: Sixteen percent of women invited joined the study and 49 completed the trial (85% retention). Reductions in weight occurred in the supervised and home-based weight control and exercise programmes; Mean (95% CI) change compared to standard care - 1.68 (- 4.36 to - 1.00), - 2.47(- 4.99 to - 0.04) Kg. Reductions in perometer assessed RAVI were seen in the supervised and home-based combined weight control and arm exercise groups and the weight stable home-based arm exercise only group: mean (95% CI) change compared to standard care - 2.4 (- 5.0 to + 0.4),- 1.8 (- 4.3 to + 0.7), - 2.5(- 4.9 to - 0.05)%. CONCLUSION: Women with BCRL and overweight and obesity engaged in diet and exercise weight loss programmes. Both weight loss/arm exercise programmes led to modest changes in weight and BCRL. Comparable reductions in BCRL were reported in the weight stable group undertaking arm exercise only. The independent and combined effects of weight loss and exercise on BCRL need further study. TRIAL REGISTRATION: ISRCTN86789850 https://doi.org/10.1186/ISRCTN86789850 , registered 2011.

The effects of short-term, progressive exercise training on disease activity in smouldering multiple myeloma and monoclonal gammopathy of undetermined significance: a single-arm pilot study.

BACKGROUND: High levels of physical activity are associated with reduced risk of the blood cancer multiple myeloma (MM). MM is preceded by the asymptomatic stages of monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) which are clinically managed by watchful waiting. A case study (N = 1) of a former elite athlete aged 44 years previously indicated that a multi-modal exercise programme reversed SMM disease activity. To build from this prior case study, the present pilot study firstly examined if short-term exercise training was feasible and safe for a group of MGUS and SMM patients, and secondly investigated the effects on MGUS/SMM disease activity. METHODS: In this single-arm pilot study, N = 20 participants diagnosed with MGUS or SMM were allocated to receive a 16-week progressive exercise programme. Primary outcome measures were feasibility and safety. Secondary outcomes were pre- to post-exercise training changes to blood biomarkers of MGUS and SMM disease activity- monoclonal (M)-protein and free light chains (FLC)- plus cardiorespiratory and functional fitness, body composition, quality of life, blood immunophenotype, and blood biomarkers of inflammation. RESULTS: Fifteen (3 MGUS and 12 SMM) participants completed the exercise programme. Adherence was 91 ± 11%. Compliance was 75 ± 25% overall, with a notable decline in compliance at intensities > 70% V̇O2PEAK. There were no serious adverse events. There were no changes to M-protein (0.0 ± 1.0 g/L, P =.903), involved FLC (+ 1.8 ± 16.8 mg/L, P =.839), or FLC difference (+ 0.2 ± 15.6 mg/L, P =.946) from pre- to post-exercise training. There were pre- to post-exercise training improvements to diastolic blood pressure (- 3 ± 5 mmHg, P =.033), sit-to-stand test performance (+ 5 ± 5 repetitions, P =.002), and energy/fatigue scores (+ 10 ± 15%, P =.026). Other secondary outcomes were unchanged. CONCLUSIONS: A 16-week progressive exercise programme was feasible and safe, but did not reverse MGUS/SMM disease activity, contrasting a prior case study showing that five years of exercise training reversed SMM in a 44-year-old former athlete. Longer exercise interventions should be explored in a group of MGUS/SMM patients, with measurements of disease biomarkers, along with rates of disease progression (i.e., MGUS/SMM to MM). REGISTRATION: https://www.isrctn.com/ISRCTN65527208 (14/05/2018).

Acute hypoxia attenuates resistance exercise-induced ribosome signaling but does not impact satellite cell pool expansion in human skeletal muscle.

Cumulative evidence supports the hypothesis that hypoxia acts as a regulator of muscle mass. However, the underlying molecular mechanisms remain incompletely understood, particularly in human muscle. Here we examined the effect of hypoxia on signaling pathways related to ribosome biogenesis and myogenic activity following an acute bout of resistance exercise. We also investigated whether hypoxia influenced the satellite cell response to resistance exercise. Employing a randomized, crossover design, eight men performed resistance exercise in normoxia (FiO2 21%) or normobaric hypoxia (FiO2 12%). Muscle biopsies were collected in a time-course manner (before, 0, 90, 180 min and 24 h after exercise) and were analyzed with respect to cell signaling, gene expression and satellite cell content using immunoblotting, RT-qPCR and immunofluorescence, respectively. In normoxia, resistance exercise increased the phosphorylation of RPS6, TIF-1A and UBF above resting levels. Hypoxia reduced the phosphorylation of these targets by ~37%, ~43% and ~ 67% throughout the recovery period, respectively (p < .05 vs. normoxia). Resistance exercise also increased 45 S pre-rRNA expression and mRNA expression of c-Myc, Pol I and TAF-1A above resting levels, but no differences were observed between conditions. Similarly, resistance exercise increased mRNA expression of myogenic regulatory factors throughout the recovery period and Pax7+ cells were elevated 24 h following exercise in mixed and type II muscle fibers, with no differences observed between normoxia and hypoxia. In conclusion, acute hypoxia attenuates ribosome signaling, but does not impact satellite cell pool expansion and myogenic gene expression following a bout of resistance exercise in human skeletal muscle.

Stuart has got the PoWeR! Skeletal muscle adaptations to a novel heavy progressive weighted wheel running exercise model in C57BL/6 mice.

Murine exercise models are developed to study the molecular and cellular mechanisms regulating muscle mass. A progressive weighted wheel running model, named 'PoWeR', was previously developed to serve as a more translatable alternative to involuntary resistance-type exercise models in rodents, such as synergist ablation. However, mice still run great distances despite the added resistance as evidenced by a large glycolytic-to-oxidative shift in muscle fibre type. Thus, PoWeR reflects a blended resistance/endurance model. In an attempt to bias PoWeR further towards resistance-type exercise, we developed a novel heavy PoWeR model (hPoWeR) utilizing higher wheel loads (max of 12.5 g vs 6 g). Adult male C57BL/6 mice voluntarily performed an 8-week progressive loading protocol (PoWeR or hPoWeR). Running distance peaked at ∼5-6 km day-1 in both treatments and was maintained by PoWeR mice, but declined in the hPoWeR mice as load increased beyond 7.5 g. Peak isometric force of the gastrocnemius-soleus-plantaris complex tended to increase in wheel running treatments. Soleus mass increased by 19% and 24% in PoWeR and hPoWeR treatments, respectively, and plantaris fibre cross-sectional area was greater in hPoWeR, compared to PoWeR. There were fewer glycolytic and more oxidative fibres in the soleus and plantaris muscles in the PoWeR treatment, but not hPoWeR. Collectively, these data suggest hPoWeR may modestly alter skeletal muscle supporting the aim of better reflecting typical resistance training adaptations, in line with decreased running volume and exposure to higher resistance. Regardless, PoWeR remains an effective hypertrophic concurrent training model in mice.

The effects of habitual resistance exercise training on cerebrovascular responses to lower body dynamic resistance exercise: A cross-sectional study.

Dynamic resistance exercise (RE) produces sinusoidal fluctuations in blood pressure with simultaneous fluctuations in middle cerebral artery blood velocity (MCAv). Some evidence indicates that RE may alter cerebrovascular function. This study aimed to examine the effects of habitual RE training on the within-RE cerebrovascular responses. RE-trained (n = 15, Female = 4) and healthy untrained individuals (n = 15, Female = 12) completed four sets of 10 paced repetitions (15 repetitions per minute) of unilateral leg extension exercise at 60% of predicted 1 repetition maximum. Beat-to-beat blood pressure, MCAv and end-tidal carbon dioxide were measured throughout. Zenith, nadir and zenith-to-nadir difference in mean arterial blood pressure (MAP) and mean MCAv (MCAvmean) for each repetition were averaged across each set. Two-way ANOVA was used to analyse dependent variables (training × sets), Bonferroni corrected t-tests were used for post hoc pairwise comparisons. Group age (26 ± 7 trained vs. 25 ± 6 years untrained, P = 0.683) and weight (78 ± 15 vs. 71 ± 15 kg, P = 0.683) were not different. During exercise average MAP was greater for the RE-trained group in sets 2, 3 and 4 (e.g., set 4: 101 ± 11 vs. 92 ± 7 mmHg for RE trained and untrained, respectively, post hoc tests all P = < 0.012). Zenith MAP and zenith-to-nadir MAP difference demonstrated a training effect (P < 0.039). Average MCAvmean and MCAvmean zenith-to-nadir difference was not different between groups (interaction effect P = 0.166 and P = 0.459, respectively). Despite RE-trained individuals demonstrating greater fluctuations in MAP during RE compared to untrained, there were no differences in MCAvmean. Regular RE may lead to vascular adaptations that stabilise MCAv during RE.

Network model of skeletal muscle cell signalling predicts differential responses to endurance and resistance exercise training.

Exercise-induced muscle adaptations vary based on exercise modality and intensity. We constructed a signalling network model from 87 published studies of human or rodent skeletal muscle cell responses to endurance or resistance exercise in vivo or simulated exercise in vitro. The network comprises 259 signalling interactions between 120 nodes, representing eight membrane receptors and eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise-induced phenotypes. Using this network, we formulated a logic-based ordinary differential equation model predicting time-dependent molecular and phenotypic alterations following acute endurance and resistance exercises. Compared with nine independent studies, the model accurately predicted 18/21 (85%) acute responses to resistance exercise and 12/16 (75%) acute responses to endurance exercise. Detailed sensitivity analysis of differential phenotypic responses to resistance and endurance training showed that, in the model, exercise regulates cell growth and protein synthesis primarily by signalling via mechanistic target of rapamycin, which is activated by Akt and inhibited in endurance exercise by AMP-activated protein kinase. Endurance exercise preferentially activates inflammation via reactive oxygen species and nuclear factor κB signalling. Furthermore, the expected preferential activation of mitochondrial biogenesis by endurance exercise was counterbalanced in the model by protein kinase C in response to resistance training. This model provides a new tool for investigating cross-talk between skeletal muscle signalling pathways activated by endurance and resistance exercise, and the mechanisms of interactions such as the interference effects of endurance training on resistance exercise outcomes.

Multimodal Exercise and Cognitive Training Program Improves Cognitive Function in Amnestic Mild Cognitive Impairment.

OBJECTIVE: To investigate the preliminary efficacy of a combined physical exercise + cognitive training intervention for older adults with amnestic mild cognitive impairment (aMCI). DESIGN: Randomized clinical trial. SETTING: Veteran Affairs Hospital, Palo Alto, CA. PARTICIPANTS: Sample included 72 community-dwelling volunteers (mean age 72.4 ± 9.5) diagnosed with aMCI. INTERVENTION: Participants were randomized to either a combined aerobic and resistance exercise + cognitive training (CARE+CT) or stretching exercise + CT (SE+CT). MEASUREMENTS: Primary outcomes included intervention specific assessments of word list and name-face recall. Secondary cognitive outcomes included standardized composite scores that reflect cognitive domains (e.g., learning and memory, executive function, processing speed, visuospatial ability, language). Secondary physiological outcomes included VO2 max and functional capacity (e.g., distance walked 6-minute walk test). APOE and BDNF were determined from whole blood samples. RESULTS: Controlling for age and employment status, linear mixed effects models revealed that all participants experienced significant improvement in the delayed recall of word list, learning and memory and executive function. Only the CARE+CT condition had significant improvement in processing speed and functional capacity. APOE4 status impacted cognitive benefits of those in the SE+CT condition. CONCLUSIONS: Results provide preliminary support for combined exercise and cognitive training interventions for older adults with aMCI. Further research is needed to understand the mechanisms involved as well as the impact of these interventions in diverse samples. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01962038.

Delivery of a telehealth supported home exercise program with dietary advice to increase plant-based protein intake in people with non-alcoholic fatty liver disease: a 12-week randomised controlled feasibility trial.

This study evaluated the feasibility and safety of a telehealth delivered exercise plus plant-based protein diet in adults with non-alcoholic fatty liver disease (NAFLD). This was a 12-week, randomised controlled feasibility trial including twenty-eight adults aged > 45 years with NAFLD randomised to a home muscle strengthening program (3 d/week) with increased protein intake (target ∼1·2-1·5 g/kg/d) from predominately plant-based sources and behavioural change support (3-4 text messages/week) (Pro-Ex n 14) or usual care (UC, n 14). Feasibility was assessed via retention (≤ 10 % attrition), adherence (exercise ≥ 66 %; recommended daily protein serves ≥ 80 %) and safety (adverse events). Secondary outcomes included macronutrient intake (3 × 24-h records), weight, moderate-to-vigorous physical activity (MVPA) and 30 s sit-to-stand (STS) performance. Study retention was 89 %. Mean exercise adherence (Pro-Ex) was 52 % with one adverse event from 241 sessions. In Pro-Ex, mean daily plant protein serves increased (0·9 to 1·4/d) and animal protein decreased (1·5 to 1·2/d) after 12-weeks, but overall adherence (serves/day) was 32[RD1] % (plant) and 42 % (animal). Relative to UC, Pro-Ex experienced a mean 2·7 (95 % CI: 0·9, 4·4) increase in 30 s STS number, 46-minute (95 % CI: -153, 245) increase in MVPA, 1·7 kg (95 % CI: -3·5, 0·2) decrease in weight, 35·2 g (95 % CI: 11·0, 59·3) increase in protein. In adults with NAFLD a telehealth home exercise and dietary intervention was safe and improved habitual plant and animal protein intake, but overall adherence was modest suggesting more intensive healthcare support may be required.

An acute bout of resistance exercise increases BDNF in hippocampus and restores the long-term memory of insulin-resistant rats.

A sedentary lifestyle, inadequate diet, and obesity are substantial risk factors for Type 2 diabetes mellitus (T2DM) development. A major picture of T2DM is insulin resistance (IR), which causes many impairments in brain physiology, such as increased proinflammatory state and decreased brain-derived neurotrophic factor (BDNF) concentration, hence reducing cognitive function. Physical exercise is a non-pharmacological tool for managing T2DM/IR and its complications. Thus, this study investigated the effects of IR induction and the acute effects of resistance exercise (RE) on memory, neurotrophic, and inflammatory responses in the hippocampus and prefrontal cortex of insulin-resistant rats. IR was induced by a high-fat diet and fructose-rich beverage. Insulin-resistant rats performed acute resistance exercise (IR.RE; vertical ladder climb at 50-100% of the maximum load) or rest (IR.REST; 20 min). Cognitive parameters were assessed by novel object recognition (NOR) tasks, and biochemical analyses were performed to assess BDNF concentrations and inflammatory profile in the hippocampus and prefrontal cortex. Insulin-resistant rats had 20% worse long-term memory (LTM) (p < 0.01) and lower BDNF concentration in the hippocampus (-14.6%; p < 0.05) when compared to non-insulin-resistant rats (CON). An acute bout of RE restored LTM (-9.7% pre vs. post; p > 0.05) and increased BDNF concentration in the hippocampus (9.1%; p < 0.05) of insulin-resistant rats compared to REST. Thus, an acute bout of RE can attenuate the adverse effects of IR on memory and neurotrophic factors in rats, representing a therapeutic tool to alleviate the IR impact on the brain.

Effects of different exercise modes and intensities on cognitive performance, adult hippocampal neurogenesis, and synaptic plasticity in mice.

Exercise can induce beneficial improvements in cognition. However, the effects of different modes and intensities of exercise have yet to be explored in detail. This study aimed to identify the effects of different exercise modes (aerobic and resistance) and intensities (low and high) on cognitive performance, adult hippocampal neurogenesis and synaptic plasticity in mice. A total of 40 C57BL/6J mice were randomised into 5 groups (n = 8 mice per group): control, low-intensity aerobic exercise, high-intensity aerobic exercise, low-intensity resistance exercise, and high-intensity resistance exercise. The aerobic exercise groups underwent treadmill training, while the resistance exercise groups underwent ladder climbing training. At the end of the exercise period, cognitive performance was assessed by the Y-maze and Barnes maze. In addition, adult hippocampal neurogenesis was evaluated immunohistochemically by 5-bromo-2'-deoxyuridine (BrdU)/ neuronal nuclei (NeuN) co-labeling. The levels of synaptic plasticity-related proteins in the hippocampus, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD-95), were analyzed by western blotting. Our results showed no significant differences in cognitive performance among the groups. However, high-intensity aerobic exercise significantly increased hippocampal adult neurogenesis relative to the control. A trend towards increased adult neurogenesis was observed in the low-intensity aerobic group compared to the control group. No significant changes in synaptic plasticity were observed among all groups. Our results indicate that high-intensity aerobic exercise may be the most potent stimulator of adult hippocampal neurogenesis.

Investigation of left atrial mechanical function and left ventricular systolic and diastolic parameters in athletes performing resistance exercise and combined exercise.

Some individuals who go to fitness centers for various purposes perform resistance exercise (RE) alone, while others engage in combined exercise (CE) by including cardio exercises along with RE. Studying the effects of these two different training methods on left ventricular (LV) systolic and diastolic parameters and left atrial mechanical function is an important step toward understanding the effects of different types of exercise on cardiac function. This knowledge has significant implications for public health, as it can inform the development of targeted and effective exercise programs that prioritize cardiovascular health and reduce the risk of adverse outcomes. Therefore, the primary aim of this study is to comprehensively investigate the LV systolic and diastolic parameters of athletes who engage in RE and CE using ECHO, to contribute to the growing body of literature on the cardiovascular effects of different types of exercise. Forty-two amateur athletes aged between 17 and 52 were included in our study. The participants consisted of the RE (n = 26) group who did only resistance exercise during the weekly exercise period, and the CE group (n = 16) who also did cardio exercise with resistance exercises. After determining sports age (year), weekly exercise frequency (day), and training volume (min) in addition to demographic information of RE and CE groups, left ventricular systolic and diastolic parameters and left atrial functions were determined by ECHO. Findings from our study revealed that parameters including the left ventricular end-diastolic diameter (LVEDD) (p = .008), left ventricular end-diastolic volume (LVEDV) (p = .020), stroke volume index (SV-I) (p = .048), conduit volume (CV-I) (p = .001), and aortic strain (AS) (p = .017) were notably higher in the RE group compared to the CE group. Also left atrial active emptying volüme (LAAEV) of CE was higher than the RE group (p = .031). In conclusion, the cardiac parameters of the RE group showed more athlete's heart characteristics than the CE group. These results may help to optimize the cardiovascular benefits of exercise routines while minimizing the potential risks associated with improper training.

Resistance exercise alleviates dexamethasone-induced muscle atrophy via Sestrin2/MSTN pathway in C57BL/6J mice.

AIM: It has long been recognized that resistance exercise can substantially increase skeletal muscle mass and strength, but whether it can protect against glucocorticoid-induced muscle atrophy and its potential mechanism is yet to be determined. This study aimed to investigate the protective effects of resistance exercise in dexamethasone-induced muscle atrophy and elucidate the possible function of exercise-induced protein Sestrin2 in this process. METHODS: Eight-week-old male C57BL/6J mice carried out the incremental mouse ladder exercise for 11 weeks. Two weeks before the end of the intervention, mice were daily intraperitoneally injected with dexamethasone. Body composition, muscle mass, and exercise performance were examined to evaluate muscle atrophy. In vitro, C2C12 cells were used for RT-qPCR, Western Blot, and immunofluorescence experiments to elucidate the potential mechanism. RESULTS: Our results showed that long-term resistance exercise is an effective intervention for dexamethasone-induced muscle atrophy. We also found that Sestrin2 plays a vital role in dexamethasone-induced muscle atrophy. In both animal (P = .0006) and cell models (P = .0266), dexamethasone intervention significantly reduced the protein expression of Sestrin2, which was increased (P = .0112) by resistance exercise. Inversely, overexpression of Sestrin2 improved (P < .0001) dexamethasone-induced myotube cell atrophy by reducing the activation of the ubiquitin-proteasome pathway via inhibiting Forkhead box O3 (FoxO3a) and myostatin (MSTN)/small mother against decapentaplegic (Smad) signaling pathways. CONCLUSION: Taken together, our results indicated that Sestrin2 may serve as an effective molecule that mimics the protective effect of resistance exercise on dexamethasone-induced muscle atrophy.