Weeks Of Exercise Training Research Articles

Abstract P206: Proteomic And Metabolomic Signatures Of Plasma Triglyceride-related Trait Responses To Regular Exercise

Introduction: Elevated plasma triglycerides (TG) are associated with risk of cardiovascular disease and are modifiable through lifestyle interventions such as regular exercise. However, TG responses to regular exercise are characterized by significant inter-individual differences. Hypothesis: We hypothesized that baseline levels of circulating proteins and metabolites are associated with TG response to exercise and can predict exercise-induced changes in plasma TG traits. Methods: We measured circulating proteins (n=4979 proteins) and metabolites (n=300) in 650 Black and White adults of the HERITAGE Family Study who completed 20 weeks of exercise training and had complete data on TG traits. We investigated two TG-related traits that significantly improved with training: fasting TG and large TG-rich lipoprotein particle concentration (LTRLP). The association between baseline analyte values and exercise-induced changes in TG traits were examined using linear mixed models adjusted for age, sex, race, BMI, baseline trait value, and the random effect of family membership. Significance was determined as FDR<0.05. Molecular signatures of TG trait responses were generated via elastic net regression tuned using leave-one-out cross validation. Results: Regular exercise significantly reduced plasma TG (-1.03±1.3 mmol/L, p=0.01) and LTRLP (-0.24±2.2 nmol/L, p= 0.007), with their training-induced changes moderately correlated (r=0.4, p<0.0001). We identified largely distinct panels of baseline analytes associated with changes in TG and LTRLP ( Table 1 ). Similarly, elastic net regression yielded distinct models of 99 analytes for TG and 315 analytes for LTRLP responses to exercise with accuracy of RMSE=1.28 mmol/L for TG and 2.16 nmol/L for the LTRLP model. Conclusions: We identified panels of proteins and metabolites associated with exercise-induced changes in TG traits and demonstrate, within our data, circulating analytes hold promise for predicting the exercise responsiveness of plasma TG-related traits.

Abstract P204: Association Of Plasma Proteome With Inflammatory Markers Crp And Glyca And Their Responses To Exercise Training

Introduction: C-reactive protein (CRP) and GlycA are established biomarkers of inflammation. Regular exercise tends to decrease CRP and GlycA levels. However, the molecules underlying CRP and GlycA and their responses to exercise training are less known. Hypothesis: We hypothesized that distinct protein signatures exist for both baseline levels and exercise responsiveness of CRP and GlycA, however with some overlap of proteins across signatures. Methods: Measures were performed before and after 20 weeks of exercise training in 652 Black and White adults from the HERITAGE Family Study. 4,979 circulating proteins were measured using SomaScan. High-sensitivity CRP was measured using automated assays. GlycA was quantified by NMR spectroscopy (LabCorp). Linear mixed models were used to test: 1) Association of baseline proteins with baseline hsCRP and GlycA and 2) Association of change in protein with changes in hsCRP and GlycA. Models were adjusted for age, sex, race, BMI, with family membership as a random variable, with change models also adjusting for baseline trait value. Significance was determined as FDR<0.05. Results: Baseline levels (r=0.51, p<0.0001) and change (r=0.31, p<0.0001) of hsCRP and GlycA were moderately correlated. hsCRP did not change with training, while GlycA trended towards decreasing (Table 1). Across time points, 388 and 1746 unique proteins were associated with hsCRP and GlycA, respectively, with substantial overlap across traits and time points (Table 1). The CRP protein was the top association in 3 of 4 models (range: 1.4x10 -40 < p < 1.2x10 -08 ), with serum amyloid A-2 and A-1 (SAA2, SAA) among the top 6 hits for 3 of 4 models (Table 1). Conclusions: More unique proteins were associated with GlycA levels at both timepoints, with most hsCRP proteins overlapping with GlycA proteins. Overall, a substantial number of proteins are associated with CRP and GlycA levels regardless of when they are measured, which has potential implications for using proteins as signatures of these inflammatory biomarkers.

Effects of exercise training on health capabilities and life satisfaction among overweight and obese African American women.

More importance has been placed on exercise training due to increase in the overweight and obese population. However, few studies have researched the effects of exercise training on the health capabilities and life satisfaction levels of overweight and obese African American women. This study sought to determine the effect of a 12-week exercise training on health capabilities and life satisfaction levels of overweight and obese African American women. Participants, who passed an initial screening and pre-assessment, were measured current health capabilities and life satisfaction levels both prior to, and following, the 12-week exercise training. The results from this study indicated an improvement in health capabilities, although with no significant differences following exercise training, while a significantly higher life satisfaction levels was observed among the overweight and obese African American women. The findings suggest that exercise training can be beneficial to enhance overweight and obese African American women's health capabilities and life satisfaction levels. Exercise professionals should provide the appropriate exercise trainings so that overweight and obese African American women can optimize life satisfaction levels.

Exercise activates autophagy and regulates endoplasmic reticulum stress in muscle of high-fat diet mice to alleviate insulin resistance

Exercise training has been demonstrated as an effective therapy for insulin resistance (IR) to relieve skeletal muscle metabolic disorders. Physiologic protective autophagy was found blocked by IR induced severe endoplasmic reticulum (ER) stress, which may lead to progression of IR. However, the mechanisms are not fully understood. Therefore, this study sought to investigate that how exercise training act on IR through an exploration into the mechanism of ER stress and high-fat diet (HFD)-blocked autophagy. A rodent model was adopted in mice via a HFD and an 8-week swim exercise training intervention. The mouse IR model was successfully established through HFD treatment: body mass, adipose weight, HOMA-IR index increased, as well as IRS1, inhibited in the muscle of HFD mice. Moreover, the AMPK/PGC1α pathway was depressed and IRE1, PERK, ATF6-related ER stress signaling was activated in the muscle of HFD mice. While autophagy factors, including BNIP3, LC3II/LC3I, and PINK1, decreased. However, additional 8-week exercise training during HFD was found to reverse all these changes and alleviate IR. Thus, exercise training could facilitate HFD-blocked protective autophagy via the activation of the AMPK/PGC1α pathway to relieve insulin resistance in mice. Our study provides experimental data for the prevention of T2DM and insulin resistance.

Assessment of cancer prevention effect of exercise.

There are many documents about benefits of exercise on human health. However, evidences indicate to positive effect of exercise on disease prevention, understanding of many aspects of this mechanism need more investigations. Determination of critical genes which effect human health.GSE156249 including 12 gene expression profiles of healthy individual biopsy from vastus lateralis muscle before and after 12-week combined exercise training intervention were extracted from gene expression omnibus (GEO) database. The significant DEGs were included in interactome unit by Cytoscape software and STRING database. The network was analyzed to find the central nodes subnetwork clusters. The nodes of prominent cluster were assessed via gene ontology by using ClueGO. Number of 8 significant DEGs and 100 first neighbors analyzed via network analysis. The network includes 2 clusters and COL3A1, BGN, and LOX were determined as central DEGs. The critical DEGs were involved in cancer prevention process.

Effect of a 12-week home-based exercise training program on aerobic capacity, muscle mass, liver and spleen stiffness, and quality of life in cirrhotic patients: a randomized controlled clinical trial

BackgroundPhysical inactivity and sarcopenia are two important predictors associated with increased morbidity and mortality in patients with cirrhosis. At present, the benefit of a home-based exercise training program is not well established in cirrhotic patients. The main objective of this study was to evaluate the effect of a 12-week home-based exercise training program on aerobic capacity in cirrhotic patients.MethodsThis is a randomized controlled study. Patients with compensated cirrhosis were randomized by a block of 4 with concealed allocation to the home-based exercise training (n = 20) or control (n = 20). Both groups received protein supplementation (9 g/day) for 12 weeks. The home-based exercise training program included several aerobic/isotonic moderate-intensity continuous training exercises for 40 min per session, at least four times a week, with a total duration of 12 weeks. The heart rate was continuously monitored using a Garmin® watch. In the control group, patients received exercise instruction without active encouragement and continuous monitoring. The primary outcome was a change in the 6-min walk test from baseline. Secondary outcomes were the difference in thigh muscle thickness, liver stiffness, spleen stiffness, and quality of life.ResultsA total of 40 patients were enrolled prospectively. The mean age was 56.3 ± 7.8 years, with a male predominance of 65%. The mean body mass index was 25.23 ± 3.0 kg/m2, and all were Child–Pugh A. Chronic hepatitis B or C was the primary cause of cirrhosis. The baseline values were a 6-min walk test of 475 ± 70 m, liver stiffness of 15.3 ± 9.3 kPa, spleen stiffness of 29.8 ± 21.7 kPa, and thigh muscle thickness (average compression index) of 0.64 ± 0.2 cm/m2. All baseline characteristics between the two groups were not different except the mean muscle mass which was significantly higher in the home-based exercise training group (p = 0.03, 95% CI 0.01 to 0.17). At the end of the study, no significant difference in the 6-min walk test was observed (p = 0.36, 95% CI −15.5 to 41.7). Liver stiffness measurement significantly improved in both groups, but no significant difference between groups was demonstrated (p = 0.77, 95% CI −1.3 to 1.8). Thigh muscle thickness was not different between groups. The fatigue domain of the quality of life index was significantly improved in the home-based exercise training group compared with the control group (p = 0.05, 95% CI 0.00 to 0.67). No adverse events occurred in a home-based exercise training program.ConclusionsA 12-week moderate-intensity home-based exercise training program in compensated cirrhotic patients significantly improved the fatigue domain of the quality of life index without an increase in adverse events. However, no benefit in terms of aerobic capacity, thigh muscle mass, liver stiffness, and spleen stiffness was demonstrated.Trial registration: Thai Clinical Trials Registry number TCTR20190926002, 26/09/2019 (Retrospectively registered).

Effects of twelve-week aerobic exercise on selected health-related physical fitness variables on Gonji preparatory school male students

The purpose of the present study was to investigate the effect of twelve-week aerobic exercise on health-related physical fitness components of grade eleven Gonjy preparatory school male students. The study employed an experimental research design. A simple random sampling method was used to select 30 sample students from the 242 total populations and classify them randomly into two equal experimental and control groups (n = 15). The Control group had participated in regular physical education one class of 40-minute per week in the school, but the experimental group participated additional three sessions per week for 60 minutes aerobic exercise training program, which comprised walking, jogging, running, rope skipping, and aerobic dance. Experimental and control groups had taken pre and post-test cardiorespiratory fitness, body composition, muscular endurance, muscular strength, and flexibility measured using cooper test, three-minute step test, using body mass index formula, siting tuck, chin up and sit & reach test respectively. The data collected from the study groups were analyzed by using Statistical Package for Social Science version 23 software and computed independent t-test and paired t-test and the level of significance was set at 0.05 levels. The results revealed in independent and paired t-test analysis of 12-week aerobic exercise training has significantly changed on cardiorespiratory fitness (p=0.001), muscular endurance (p=0.001) flexibility (independent p=0.04 paired p=0.02), and body mass index (p=0.001). But no significant change was observed on muscular strength in experimental and control groups of independent t-test (p=0.534 and p=0.41) and paired t-test (p=0.43 and p=0.33). Based on the finding, it was concluded that the 12 weeks aerobic exercise training program for three days per week schedule has been advantageous for the improvement of students’ health-related physical fitness variables. 
 
 
 

Changes of Physical Function and Quality of Life in Patients with Type 2 Diabetes after Exercise Training in a Municipality or a Hospital Setting.

Introduction The aim was to compare changes in physical function and quality of life (QOL) after an exercise training programme to patients with type 2 diabetes mellitus (T2DM) in a municipality and a hospital setting and to compare the patients' physical function and QOL with an age- and sex-matched general population. Methods Patients with T2DM were stratified to exercise training in a municipality (n = 26) or a hospital (n = 46), respectively. The training was one hour twice weekly for 12 weeks. The outcomes were physical function (30 sec chair stand test (CST)) and QOL (using the SF-36). The data for the general population were collected from previous reference studies. Results Fifty-one (71%) participants completed the intervention. The CST results improved in both groups with no difference between the municipality and hospital groups (1.6 [0.1; 3.1] vs. 3.5 [2.3; 4.8] no., respectively, p = 0.062). The QOL scales physical function and general health increased more in the municipality group than in the hospital group (10.5 [2.8; 18.2] vs. -1.2 [-7.9; 5.5], respectively, p = 0.031, and 8.3 [2.3; 14.4] vs. -0.2 [-5.6; 5.1], respectively, p = 0.042). Dropout (n = 21) during the intervention was associated with reduced QOL at baseline. The patients' CST results at baseline were reduced compared to the general population (11.8 ± 3.5vs.18.9 ± 3.3, respectively, p < 0.001). All QOL scales apart from social function were reduced in the patients compared to the general population. Conclusion Patients in a 12-week exercise training programme in a hospital or a municipality setting had significantly lower QOL compared to an age- and sex-matched population sample. Similar improvements in physical function were observed in patients after completion of the exercise programme irrespective of exercise setting, whereas patient exercising in a municipality setting had higher positive changes in QOL than patients undergoing the same exercise programme in a hospital setting.

The effect of a low carbohydrate ketogenic diet with or without exercise on postpartum weight retention, metabolic profile and physical activity performance in postpartum mice

The present study examined the effect of the isocaloric low-carbohydrate ketogenic diet (LCKD) with or without exercise training for 6 weeks on postpartum weight retention (PPWR), body composition, metabolic profile and physical activity performance in postpartum mice. Postpartum mice were assigned to four groups (n=8/group) as follows: (1) those on a control diet without aerobic exercise (CN); (2) those on a control diet with aerobic exercise (CN+EX), (3); those on a LCKD without aerobic exercise (LCKD); (4) those on a LCKD with aerobic exercise (LCKD+EX). CN+EX and LCKD+EX mice performed 6 weeks of exercise training on a treadmill. After the 6-week intervention, physical activity performance was determined. Postpartum mice in all groups experienced progressive reductions in body weight over the study period. The LCKD group had the smallest reduction in PPWR (P<.05). The LCKD group had significantly higher total cholesterol, low-density lipoprotein cholesterol and lactate dehydrogenase levels, and liver lipid concentrations with a worsened glucose tolerance, compared to the CN group (P<.05). The LCKD group showed significant reductions in physical activity performance, whilst the LCKD+EX group showed significant improvement in endurance performance, and paralleled the concomitant elevation in blood ketone levels. Six-week LCKD feeding on its own was less effective for reducing PPWR, and more detrimental to the postpartum metabolic outcomes and physical activity performance of the postpartum mice. The feasibility of a LCKD with or without exercise during the postpartum period as a strategy for managing PPWR and improving postpartum metabolic profiles should be carefully considered.

Uticaj fizičkog treninga na markere inflamacije kod bolesnika sa koronarnom arterijskom bolešću

Aim. To evaluate the influence of exercise training on inflammatory markers and exercise tolerance in coronary artery disease (CAD) patients. Patients and methods. A total of 54 subjects were enrolled in the present study, including 34 CAD patients (CAD group: 59.2 ± 8.2 years) and 20 healthy controls (C group: 54.2 ± 8.0 years). C reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC), and placental growth factor (PIGF) were determined, and an exercise test was performed in both groups at baseline and once again in CAD group after the supervised 3 weeks of aerobic exercise training. Results. At baseline, CRP, ESR and PIGF were significantly higher in the CAD group compared to the C group (p = 0.038, p = 0.019 and p = 0.002), while exercise capacity was significantly higher in the C group (p ˂ 0.01). After 3 weeks of exercise training, CRP, ESR, WBC count and PIGF significantly decreased (p = 0.048, p ˂ 0.001, p = 0.002 and p ˂ 0.001 respectively), while exercise capacity significantly increased (p ˂ 0.001) in the CAD group. In the CAD group, CRP decrease significantly correlated with WBC and PIGF decrease (r = 0.816, p = 0.002 and r = 0.988, p ˂ 0.001), as well as with exercise capacity increase (r = 0.834, p ˂ 0.001). Also, WBC decrease significantly correlated both with PIGF decrease (r = 0.768, p ˂ 0.001) and exercise capacity increase (r = 0.548, p = 0.012), while PIGF decrease significantly correlated with exercise capacity increase (r = 0.548, p = 0.013). Conclusion. Residential exercise training in CAD patients reduces inflammation, expressed through a significant decrease in CRP, ESR, WBC count and PIGF levels. Those positive changes in inflammatory markers are associated with significant improvement in exercise capacity.

Baseline Body Mass Index Influences the Responses to Exercise Training on Quality of Life in Women with Obesity

Purpose: Exercise has been documented as a critical strategy for improving physical and mental health. However, the impact of exercise training (ET) on quality of life (QoL) among obese is controversial. The present study aims to evaluate the impact of a 20-week ET program in women with obesity and the influence of baseline weight status on QoL responses to the ET program. Methods: This secondary analysis from a quasi-experimental study included 40 obese women (BMI &gt;30 kg/m2) aged between 18 and 65 years old (20 interventions and 20 controls). The intervention group participated in a moderate-to-vigorous intensity ET thrice a week, nutritional guidance, and psychological support. The control group received the same activities of nutritional guidance and psychological support but did not perform the ET. Measurements of QoL (WHOQOL-Bref) were performed at baseline and after 20- week follow-up. Results: No significant impact of 20-week ET on QoL among obese women was observed. However, greater improvements in physical health, psychological, social relationship, and environment domains were observed for every increase in 1 unit of baseline BMI, except for the overall QoL score. Conclusions/Recommendation: We can speculate that the better QoL responses to ET among those with higher BMI at baseline may be explained by the fact that individuals with more severe obesity are more impacted by functional limitations, stigmatization, discrimination, and social isolation; therefore, presenting worse QoL.

The interactive effects of exercise training and functional feeds on the cardiovascular performance of rainbow trout (Oncorhynchus mykiss) at high temperatures.

The cardiovascular performance of salmonids in aquaculture can be impaired by acute climate warming, posing risks for fish survival. Exercise training and functional feeds have been shown to be cardioprotective in mammals but their action on the fish heart and its upper thermal performance has not been studied. To investigate this, rainbow trout were trained at a moderate water velocity of 1 body length per second (bl s−1) for 6 h per day, either alone or in combination with one of two functional feed-supplements, allicin and fucoidan. After 6 weeks of exercise training and feeding, maximum heart rate and the temperature coefficient of heart rate were significantly higher in the trained fish as compared to untrained ones. There was a slight increase in hematocrit in trained control fish reared on a normal diet (TC group) compared to untrained fish fed with the same diet (CC). This implies that exercise training enhanced oxygen delivery to trout tissues via an increase of cardiac blood flow in warm water. However, cardiac thermal tolerance was not affected by exercise training or feeding, except from the temperature of peak heart rate which was higher in the trained group fed with fucoidan supplement (TF) as compared to the untrained group fed with same diet (CF). Allicin supplement caused a significant reduction in the maximum heart rate and the temperature coefficient of heart rate, especially in trained fish, while fucoidan supplement did not cause any effect on heart rate. No differences were observed in growth performance among groups. However, fish fed with fucoidan-supplemented diet had a slight reduction in feed conversion efficiency. We suggest further investigations to understand the antagonistic effect of allicin supplemental feeding and exercise training on cardiovascular performance. More studies are also required to investigate if other exercise training intensities could increase cardiac thermal tolerance.

Balance training in individuals with Parkinson's disease: Biodex Stability System versus supervised exercise program

OBJECTIVE: The objective of this study was to evaluate the effect of balance training, using the Biodex Stability System (BSS) or supervised exercises, on balance and gait in individuals with Parkinson's disease (PD).DESIGN: This was a prospective, pilot interventional cohort study.PARTICIPANTS: Twenty individuals with PD at Hoehn and Yahr stages I–III were included in the study.INTERVENTIONS: Ten subjects in the BSS group and 10 subjects in the non-BSS group (supervised balance exercise training without BSS) participated in 55-min exercise sessions 3 times a week for 4 weeks.OUTCOME MEASUREMENTS: Postural sway measures-sway area, anterior-posterior (AP) and medial-lateral (ML) center of pressure path length, and root mean square velocity in AP and ML directions were collected at baseline and postintervention. Secondary outcome measures of the Berg Balance Scale (BBS), spatiotemporal gait measures-gait velocity, step length, and stride length, Timed Up and Go, and 6-min walk test data were also collected at baseline and postexercise intervention for both the groups.RESULTS: Improvements in postural sway were seen in the BSS group postintervention (sway area mean change = −435.3 mm2; 95% confidence interval = −818.5, −52.2). Postural sway data from the non-BSS group were unavailable, due to a technical failure. All secondary outcome measures improved in both the groups; however, we did not find any significant between-group differences in any of the secondary measures.CONCLUSIONS: A 4-week exercise training using BSS improved measures of balance and gait in individuals with PD. However, improvements were also seen after an exercise program that did not use BSS. This suggests that at least for the measures used in this study, there were no differences between BSS training and supervised exercise balance training.

Effect of 12-Week Aerobic Exercise Training on Chemokine Ligands and Their Relative Receptors in Balb/C Mice with Breast Cancer

Background: Some chemokines like C C motif chemokine ligand (CCL) 2 and 5 and their receptors (CCR) 2 and 5 are mediators of chronic inflammation and cancer development. Moreover, physical exercise can increase the activity of antioxidant enzymes. However, its effect on cancer cells has not been reported at present. Objectives: Therefore, the present study aimed to ascertain the effect of 12-week aerobic exercise training (AET) on CCL2, CCR2, CCL5, and CCR5 in mice with breast cancer. Methods: Sixteen Balb/c mice aged 4 - 5 weeks (n = 16; approximate weight: 18 ± 2 g) were divided into two groups: AET group (AETG) and control group (CG) (n = 8 per group). The AETG performed 12-week treadmill running at 18 m/min for 40 min and five times a week. Plasma levels of CCL2 and CCL5 were measured by ELISA, and the CCR2 and CCR5 were evaluated by Western blotting. Two independent sample t-test was applied to compare the differences between AETG and CG. Results: The analysis displayed after 12 weeks showed a significant reduction in AETG compared to CG in CCL2 (3.94 ± 1.12 vs. 15.40 ± 3.29 pg/mL; P = 0.001), CCR2 (0.56 ± 0.19 vs. 1.00 ± 0.001; P = 0.002), CCL5 (138.59 ± 15.72 vs. 267.57 ± 49.06 ng/mL; P = 0.001) and CCR5 (0.36 ± 0.12 vs. 1.00 ± 0.001; P = 0.001), respectively. Conclusions: We concluded that one of the main mechanisms of a positive effect of exercise on breast cancer is reducing the inflammation via CCL2 and CCL5 and their related receptors CCR2 and CCR5, respectively. Since these molecules can be triggered off oxidative stress and tumorigenesis, these results can pave the way for further studies in this field.

Effect of a 12-Week Mixed Training on Body Quality in People Living with HIV: Does Age and HIV Duration Matter?

The impact of HIV duration on exercise adaptations has not yet been studied. Moreover, the age at which subjects living with HIV are the most responsive to exercise is not clear. Investigate the effect of a mixed exercise training program on physical performance changes in individuals living with HIV and explore if age or HIV duration influence these adaptations in men. In this feasibility study, participants followed a 12-week mixed exercise training program, three times/week, 45 min/session. Physical performance including functional capacities (normal 4-m walking test, 6min walking test), grip strength (hand dynamometer), muscle power, body composition (android and gynoid fat masses, appendicular lean mass) were evaluated pre- and post-intervention. Subgroup analysis according to the median age of the participants (age<50yrs vs. age≥50yrs) and median HIV duration (HIV<20yrs vs. HIV≥20yrs) were performed in men. A total of 27 participants (age: 54.5±6.8yrs, men: 85%; HIV duration: 19.3±7.6yrs) were included. At the end of the intervention, significant increases compared to baseline were seen in grip strength (p=0.017), leg power (p<0.001), normal walking speed (p<0.001) and 6-min walking distance (p=0.003). Following the intervention, parameters improved similarly in both age groups. However improvement was greater in those with HIV>20yrs than those with a shorter infection duration, with change (%) on total (p<0.001), android (p=0.02), and gynoid (p=0.05) fat masses as well as appendicular lean mass index (p=0.03). Mixed exercise training seems to be an effective intervention to improve physical performance in individuals living with HIV. In addition, this study suggests that neither age nor HIV duration has influence on the effect of mixed training in this population.

The Effect of Structured Exercise Compared with Education on Neuropathic Signs and Symptoms in People at Risk of Neuropathic Diabetic Foot Ulcers: A Randomized Clinical Trial.

Background and Objectives: Lifestyle interventions such as exercise prescription and education may play a role in the management of peripheral neuropathy in people with diabetes. The aim of this study was to determine the effect of undertaking an exercise program in comparison with an education program on the signs and symptoms of peripheral neuropathy in people with diabetes at risk of neuropathic foot ulceration. Materials and Methods: Twenty-four adult participants with diabetes and peripheral neuropathy were enrolled in this parallel-group, assessor blinded, randomised clinical trial. Participants were randomly allocated to one of two 8-week lifestyle interventions, exercise or education. The primary outcome measures were the two-part Michigan Neuropathy Screening Instrument (MNSI) and vibratory perception threshold (VPT). Secondary outcome measures included aerobic fitness, balance and lower limb muscular endurance. Results: Participants in both lifestyle interventions significantly improved over time for MNSI clinical signs (MD: −1.04, 95% CI: −1.68 to −0.40), MNSI symptoms (MD: −1.11, 95% CI: −1.89 to −0.33) and VPT (MD: −4.22, 95% CI: −8.04 to −0.40). Although the interaction effects did not reach significance, changes in values from pre to post intervention favoured exercise in comparison to control for MNSI clinical signs (MD −0.42, 95% CI −1.72 to 0.90), MNSI clinical symptoms (MD −0.38, 95% CI −1.96 to 1.2) and VPT (MD −4.22, 95% CI −12.09 to 3.65). Conclusions: Eight weeks of exercise training or lifestyle education can improve neuropathic signs and symptoms in people with diabetes and peripheral neuropathy. These findings support a role for lifestyle interventions in the management of peripheral neuropathy.

Metabolic Adaptations to Aerobic Exercise in Aged Mice

Aerobic exercise training is a potent intervention for the treatment and prevention of age-related disease, such as heart disease, obesity, and Type 2 Diabetes. Insulin resistance, a hallmark of Type 2 Diabetes, is reversed in response to aerobic exercise training. However, the effect of aerobic exercise training on glucagon sensitivity is unclear. Glucagon signaling at the liver promotes fatty acid oxidation, inhibits De novo lipogenesis, and activates AMP Kinase, a key mediator of healthy aging. Like humans, aging in mice age leads to a decline in physical and metabolic function. To understand the role of glucagon signaling in exercise-induced improvements in physical and metabolic function in the mouse, we implemented a 16-week aerobic exercise training protocol in young and aged mice. 16 weeks of exercise training initiated at 6 months of age increased markers of physical function (P<0.01) and attenuated age-related weight gain (P<0.05) and fat mass (P<0.0001). Additionally, exercise training improved glucose clearance (P<0.01), enhanced glucose-stimulated insulin secretion (P<0.01) and decreased hepatic lipid accumulation (P<0.05). Importantly, exercise training decreased hypoglycemia stimulated glucagon secretion (P<0.01), with no effect on hepatic glucagon receptor mRNA expression or serum glucagon. Thus, we propose that aerobic exercise training enhances glucagon sensitivity at the liver, implicating glucagon as a potential mediator of exercise-induced improvements in aging. Studies initiating the same aerobic exercise training intervention at 18 months of age in the mouse are currently underway to establish the role of glucagon receptor signaling in exercise-induced improvements in aging.

Inflammation and physical dysfunction: responses to moderate intensity exercise in chronic kidney disease.

People with chronic kidney disease (CKD) experience skeletal muscle wasting, reduced levels of physical function and performance, and chronic systemic inflammation. While it is known that a relationship exists between inflammation and muscle wasting, the association between inflammation and physical function or performance in CKD has not been well studied. Exercise has anti-inflammatory effects, but little is known regarding the effect of moderate intensity exercise. This study aimed to (i) compare systemic and intramuscular inflammation between CKD stage G3b-5 and non-CKD controls; (ii) establish whether a relationship exists between physical performance, exercise capacity and inflammation in CKD; (iii) determine changes in systemic and intramuscular inflammation following 12 weeks of exercise; and (iv) investigate whether improving inflammatory status via training contributes to improvements in physical performance and muscle mass. This is a secondary analysis of previously collected data. CKD patients stages G3b-5 (n=84, n=43 males) and non-CKD controls (n=26, n=17 males) underwent tests of physical performance, exercise capacity, muscle strength and muscle size. In addition, a subgroup of CKD participants underwent 12 weeks of exercise training, randomized to aerobic (AE, n=21) or combined (CE, n=20) training. Plasma and intramuscular inflammation and myostatin were measured at rest and following exercise. Tumour necrosis factor-α was negatively associated with lower $^{^{^{.}}}{\rm V}$O2Peak (P=0.01), Rectus femoris-cross sectional area (P=0.002) and incremental shuttle walk test performance (P<0.001). Interleukin-6 was negatively associated with sit-to-stand 60 performances (P=0.006) and hand grip strength (P=0.001). Unaccustomed exercise created an intramuscular inflammatory response that was attenuated following 12 weeks of training. Exercise training did not reduce systemic inflammation, but AE training did significantly reduce mature myostatin levels (P=0.02). Changes in inflammation were not associated with changes in physical performance. Systemic inflammation may contribute to reduced physical function in CKD. Twelve weeks of exercise training was unable to reduce the level of chronic systemic inflammation in these patients, but did reduce plasma myostatin concentrations. Further research is required to further investigate this.

Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of 2 randomized, clinical trials.

Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant individuals and a double-blind, cross-over trial conducted in 15 healthy lean males) were included in this paper. In both studies, the effect of acute exercise ± metformin treatment on different skeletal muscle variables, previously suggested to be involved in a pharmaco-physiological interaction between metformin and exercise, was assessed. Furthermore, in the parallel-group trial, the effect of 12 weeks of exercise training was assessed. Skeletal muscle biopsies were obtained before and after acute exercise and 12 weeks of exercise training, and mitochondrial respiration, oxidative stress and AMPK activation was determined. Metformin did not significantly affect the effects of acute exercise or exercise training on mitochondrial respiration, oxidative stress or AMPK activation, indicating that the response to acute exercise and exercise training adaptations in skeletal muscle is not affected by metformin treatment. Further studies are needed to investigate whether an interaction between metformin and exercise is present in other tissues, e.g., the gut. Trial registration: ClinicalTrials.gov (NCT03316690 and NCT02951260). Novelty: Metformin does not affect exercise-induced alterations in mitochondrial respiratory capacity in human skeletal muscle. Metformin does not affect exercise-induced alterations in systemic levels of oxidative stress nor emission of reactive oxygen species from human skeletal muscle. Metformin does not affect exercise-induced AMPK activation in human skeletal muscle.

Abstract 14259: Exercise Training Attenuates Activin Type II Receptor Signaling in the Aged Heart

Introduction: Exercise training (ExT) improves functional capacity in older adults with heart failure (HF). However, the molecular mechanisms by which ExT exerts these benefits are unclear. We previously showed that cardiac activin type II receptor (ActRII) signaling increases in aging and HF, and that ActRII inhibition can improve cardiac exercise capacity in aged C57BL/6 mice, a model of age-related HFpEF. Whether cardiac ActRII signaling is modulated by ExT is unknown. Hypothesis: We hypothesized that ExT would attenuate cardiac ActRII signaling in aged mice. Methods: A moderate intensity ExT protocol (treadmill running, 10m/min, 10° incline, 45min/day, 8 weeks) was performed in 25month-old (mo) female C57BL/6 mice (OE). Functional (exercise capacity), molecular, and gravimetric assessments of HF were compared to young (YS, 4mo) and old (OS, 27mo) sedentary controls, along with indicators of downstream ActRII signaling (FSTL3 expression, SMAD3 phosphorylation, senescence, apoptosis markers). Results: After 8 weeks of ExT, exercise capacity increased in OE mice by 2.5±9.9% versus -24.1±4.6% in OS mice (p=0.05). ExT did not induce significant changes in cardiac hypertrophy or natriuretic peptide expression in aged mice, but decreased lung weight to body weight ratios (3.8±0.2(YS) vs 7.4±0.7(OS) vs 5.3±0.4(OE) mg/g, p=0.001). Cardiac ActRII signaling increased with aging and was attenuated with ExT (FSTL3/GAPDH: 1.0±0.01(YS) vs. 2.9±0.1(OS) vs. 1.0±0.2(OE) p=0.01; pSMAD3/SMAD3: 0.8±0.2(YS) vs. 1.5±0.04(OS) vs. 1.1±0.1(OE), p=0.1). Moreover, parallel changes occurred in markers of cardiac senescence (p16: 1.0±0.02(YS) vs. 1.6±0.1(OS) vs. .3±0.02(OE), p=0.02) and apoptosis (BAX: 0.8±0.2(YS) vs. 1.8±0.05(OS) vs. 1.1±0.1(OE), p=0.0007; cleaved caspase 3: 0.8±0.01(YS) vs. 2.2±0.01(OS) vs. 1.0±0.02(OE), p=0.0001), which have been shown to be regulated by ActRII signaling. Conclusions: These findings suggest aerobic ExT attenuates the cardiac ActRII signaling observed in aged mice and slows the age related decline in exercise capacity. Age-associated pathologies linked to ActRII signaling, including cellular senescence and apoptosis, were similarly modulated by ExT.