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Effects of Exercise Intervention on Mitochondrial Stress Biomarkers in Metabolic Syndrome Patients: A Randomized Controlled Trial.

ABSTRACT: Metabolic syndrome (MetS) pathogenesis involves oxidative stress associated with mitochondrial dysfunction, which triggers integrated stress responses via various compensatory metabolic modulators like mitokines and hepatokines. However, the regulatory mechanisms underlying the exercise-derived benefits with respect to mitokines and hepatokines (potential MetS biomarkers) are unknown. Thus, we investigated the effects of exercise training on MetS biomarkers and their associations with clinical parameters. In this single-center trial, 30 women with MetS were randomly assigned to 12-week supervised exercise or control groups (1:1) and compared with 12 age-matched healthy volunteers. All participants completed the study except one subject in the control group. Expectedly, serum levels of the mitokines, fibroblast growth factor-21 (FGF21), growth differentiation factor-15 (GDF15), and the hepatokine, angiopoietin-like 6 (ANGPTL6), were higher in MetS patients than in healthy volunteers. Moreover, their levels were markedly attenuated in the exercise group. Further, exercise-mediated changes in serum FGF21 and GDF15 correlated with changes in the homeostasis model of assessment of insulin resistance (HOMA-IR) and appendicular lean mass (ALM), respectively. Additionally, changes in serum triglycerides and ANGPTL6 were correlated with changes in leptin. Aberrant mitokine and hepatokine levels can be rectified by relieving metabolic stress burden. Therefore, exercise training may reduce the need for the compensatory upregulation of MetS metabolic modulators by improving gluco-lipid metabolism.

SUBMITTER: Chang JS

PROVIDER: S-EPMC7956208 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Effects of Exercise Intervention on Mitochondrial Stress Biomarkers in Metabolic Syndrome Patients: A Randomized Controlled Trial.

Chang Jae Seung JS Namkung Jun J

International journal of environmental research and public health 20210224 5

Metabolic syndrome (MetS) pathogenesis involves oxidative stress associated with mitochondrial dysfunction, which triggers integrated stress responses via various compensatory metabolic modulators like mitokines and hepatokines. However, the regulatory mechanisms underlying the exercise-derived benefits with respect to mitokines and hepatokines (potential MetS biomarkers) are unknown. Thus, we investigated the effects of exercise training on MetS biomarkers and their associations with clinical p ...[more]

PMID: 33668309

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Project description:BACKGROUND: Intensive lifestyle intervention significantly reduces the progression to diabetes in high-risk individuals. OBJECTIVE: It is not known whether a program of moderate intervention might effectively reduce metabolic abnormalities in the general population. DESIGN: Two-arm randomized controlled 1-year trial. PATIENTS: Three hundred and thirty-five patients participated from a dysmetabolic population-based cohort of 375 adults aged 45-64 years in northwestern Italy. MEASUREMENTS: We compared the effectiveness of a general recommendation-based program of lifestyle intervention carried out by trained professionals versus standard unstructured information given by family physicians at reducing the prevalence of multiple metabolic and inflammatory abnormalities. RESULTS: At baseline, clinical/anthropometric/laboratory and lifestyle characteristics of the intervention (n = 169) and control (n = 166) groups were not significantly different. The former significantly reduced total/saturated fat intake and increased polyunsaturated fat/fiber intake and exercise level compared to the controls. Weight, waist circumference, high-sensitivity C-reactive protein, and most of the metabolic syndrome components decreased in the intervention group and increased in the controls after 12 months. Lifestyle intervention significantly reduced metabolic syndrome (odds ratio [OR] = 0.28; 95% CI 0.18-0.44), with a 31% (21-41) absolute risk reduction, corresponding to 3.2 (2-5) patients needing to be treated to prevent 1 case after 12 months. The intervention significantly reduced the prevalence of central obesity (OR = 0.33; 0.20-0.56), and hypertriglyceridemia (OR = 0.48; 0.31-0.75) and the incidence of diabetes (OR = 0.23; 0.06-0.85). CONCLUSION: A lifestyle intervention based on general recommendations was effective in reducing multiple metabolic/inflammatory abnormalities. The usual care by family physicians was ineffective at modifying progressive metabolic deterioration in high-risk individuals.

Project description:Aims/hypothesis: Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of the metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to identify whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. Methods: We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. A total of 21 individuals diagnosed with the metabolic syndrome was randomly assigned for caloric restriction (CR; n = 11, mean age 49 ± 8.5 years, female 63%; diet of 5,941 ± 686 KJ per day) or isocaloric dietary protein restriction (PR; n = 10, mean age 51.6 ± 8.9 years, female 50%; diet of 8,409 ± 2,360 KJ per day) and followed for 27 days. Results: Like CR, PR promoted weight loss (-6.6%, P= 0.0041) due to reduction in adiposity (-9.9%, P= 0.0007), associated with reductions in blood glucose (-52.7%, P= 0.0002), lipid levels (cholesterol, -35.4%, P= 0.0010; triglycerides, -39.5% P= 0.0022) and blood pressure (systolic, -37.7 P< 0.0001; diastolic, -73.2% P< 0.0001). PR resulted in enrichment of metabolic pathways related to the immune system such as B cell proliferation, lymphocyte proliferation and leukocyte proliferation in subcutaneous adipose tissue. Hence, a reduction in calorie intake or changes in the gut microbiome are not necessary to confer the metabolic benefits of DR. Instead, a reduction in protein intake with a mild increase in carbohydrate intake to maintain the isocaloric balance of the diet is sufficient to improve metabolic control. Conclusions/interpretation: Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has greater potential to be used as adjuvant therapy for people with the metabolic syndrome.

Project description:ObjectivesWomen have a higher prevalence of metabolic syndrome than their male counterparts, and interventions should target women with or at risk for metabolic syndrome. The objective of this study was to compare two intervention strategies on long-term outcomes following the completion of an exercise intervention.MethodsTwenty-six women (M age = 43.35 ± 9.03) with at least one risk factor for metabolic syndrome were randomized into either a motivational interviewing group (n = 10) or self-regulation-based mobile messaging control group (n = 16) as a 12-week follow-up to a 10-week, 30-session exercise intervention. Outcomes of interest were body fat percentage, bone mineral density, waist circumference, systolic blood pressure, diastolic blood pressure, triglycerides, high-density cholesterol, and fasting blood glucose.ResultsMixed ANOVAs revealed a significant effect for group × time for body fat percentage F(1, 24) = 8.30, p = 0.01, ηp2 = 0.26, bone mineral density F(1, 24) = 6.68, p = 0.02, ηp2 = 0.22, waist circumference F(1, 24) = 10.35, p = 0.01, ηp2 = 0.30, triglycerides F(1, 24) = 5.06, p = 0.03, ηp2 = 0.17, and systolic blood pressure F(1, 24) = 5.39, p = 0.03, ηp2 = 0.18 all in favor of the motivational interviewing group after 12 weeks when compared to the self-regulation-based mobile messaging group. No significant effect for group × time was noted for diastolic blood pressure p = 0.36, ηp2 = 0.04, high-density cholesterol p = 0.08, ηp2 = 0.12, or fasting blood glucose p = 0.85, ηp2 = 0.01 when comparing the motivational interviewing and self-regulation-based mobile messaging groups.ConclusionsMotivational interviewing may be a more impactful solution to extend the effects of exercise intervention studies compared to a self-regulation-based mobile messaging control group. Future interventions should focus on increasing sample size, utilizing more objective measures of body composition, utilizing booster sessions, and increasing the length of follow-up periods.

Project description:Purpose Metabolic syndrome is associated with an increased risk of cardiovascular disease, type 2 diabetes, and breast cancer recurrence in survivors of breast cancer. This randomized controlled trial assessed the effects of a 16-week combined aerobic and resistance exercise intervention on metabolic syndrome, sarcopenic obesity, and serum biomarkers among ethnically diverse, sedentary, overweight, or obese survivors of breast cancer. Methods Eligible survivors of breast cancer (N = 100) were randomly assigned to exercise (n = 50) or usual care (n = 50). The exercise group participated in supervised moderate-to-vigorous-65% to 85% of heart rate maximum-aerobic and resistance exercise three times per week for 16 weeks. Metabolic syndrome z-score (primary outcome), sarcopenic obesity, and serum biomarkers were measured at baseline, postintervention (4 months), and 3-month follow-up (exercise only). Results Participants were age 53 ± 10.4 years, 46% were obese, and 74% were ethnic minorities. Adherence to the intervention was 95%, and postintervention assessments were available in 91% of participants. Postintervention metabolic syndrome z-score was significantly improved in exercise versus usual care (between-group difference, -4.4; 95% CI, -5.9 to -2.7; P < .001). Sarcopenic obesity (appendicular skeletal mass index, P = .001; body mass index, P = .001) and circulating biomarkers, including insulin ( P = .002), IGF-1 ( P = .001), leptin ( P = .001), and adiponectin ( P = .001), were significantly improved postintervention compared with usual care. At 3-month follow-up, all metabolic syndrome variables remained significantly improved compared with baseline in the exercise group ( P < .01). Conclusion Combined resistance and aerobic exercise effectively attenuated metabolic syndrome, sarcopenic obesity, and relevant biomarkers in an ethnically diverse sample of sedentary, overweight, or obese survivors of breast cancer. Our findings suggest a targeted exercise prescription for improving metabolic syndrome in survivors of breast cancer and support the incorporation of supervised clinical exercise programs into breast cancer treatment and survivorship care plans.

Project description:BackgroundSocietal measures to contain the spread of COVID-19 (eg, lockdown and contact restrictions) have been associated with decreased health and well-being. A multitude of prepandemic studies identified the beneficial effects of physical exercise on both physical and mental health.ObjectiveWe report on the feasibility of a remote physical exercise intervention and its stress-buffering potential in 2 untrained cohorts: a pre-COVID-19 cohort that completed the intervention in 2019 and a lockdown cohort that started the intervention shortly before pandemic-related restrictions were implemented.MethodsIn a randomized controlled trial, participants were assigned to either an intervention group (IG; pre-COVID-19 cohort: n=7 and lockdown cohort: n=9) or a control group (CG; pre-COVID-19 cohort: n=6 and lockdown cohort: n=6). IG participants received weekly individualized training recommendations delivered via web-based support. The intervention period was initially planned for 8 weeks, which was adhered to in the pre-COVID-19 cohort (mean 8.3, SD 0.5 weeks) but was extended to an average of 17.7 (SD 2.0) weeks in the lockdown cohort. Participants' health parameters were assessed before and after the intervention: aerobic capacity was measured as peak oxygen uptake (VO2peak) via cardiopulmonary exercise testing. Depressive symptoms were scored via the depression subscale of the Brief Symptom Inventory-18.ResultsDropout rates were low in both cohorts in the IG (pre-COVID-19 cohort: n=0, 0% and lockdown cohort: n=2, 16.7%) and the CG (pre-COVID-19 cohort: n=0, 0% and lockdown cohort: n=2, 20%). The mean adherence to the training sessions of the IG for both cohorts was 84% (pre-COVID-19 cohort: SD 5.5% and lockdown cohort: SD 11.6%). Aligned rank transform ANOVAs in the lockdown cohort indicated deterioration of VO2peak and depressive symptoms from before to after the intervention in the CG but no longitudinal changes in the IG. Analyses in the pre-COVID-19 cohort revealed significant increases in VO2peak for the IG compared to the CG (P=.04) but no intervention effects on depressive symptoms.ConclusionsWith low dropout rates and high adherence, the remote intervention was feasible for healthy adults under regular conditions and in the face of pandemic-related stressors. Moreover, our results hint at a stress-buffering effect as well as a buffering of a lockdown-induced deconditioning of remote physical exercise interventions in the pandemic scenario, which can be used in future studies to overcome equally stressful periods of life. However, due to limited statistical power, these findings should be replicated in similar scenarios.Trial registrationGerman Clinical Trials Register DRKS00018078; https://drks.de/search/en/trial/DRKS00018078.

Dataset Information

Effects of Exercise Intervention on Mitochondrial Stress Biomarkers in Metabolic Syndrome Patients: A Randomized Controlled Trial.

Publications

Effects of Exercise Intervention on Mitochondrial Stress Biomarkers in Metabolic Syndrome Patients: A Randomized Controlled Trial.

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