Exercise confers numerous salutary effects that extend beyond individual organ systems to provide systemic health benefits. Here, we discuss the role of exercise in cardiovascular health. We ...summarize major findings from human exercise studies in cardiometabolic disease. We next describe our current understanding of cardiac-specific substrate metabolism that occurs with acute exercise and in response to exercise training. We subsequently focus on exercise-stimulated circulating biochemicals ("exerkines") as a paradigm for understanding the global health circuitry of exercise, and discuss important concepts in this emerging field before highlighting exerkines relevant in cardiovascular health and disease. Finally, this Review identifies gaps that remain in the field of exercise science and opportunities that exist to translate biologic insights into human health improvement.
Exerkines in health, resilience and disease Chow, Lisa S; Gerszten, Robert E; Taylor, Joan M ...
Nature reviews. Endocrinology,
05/2022, Letnik:
18, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The health benefits of exercise are well-recognized and are observed across multiple organ systems. These beneficial effects enhance overall resilience, healthspan and longevity. The molecular ...mechanisms that underlie the beneficial effects of exercise, however, remain poorly understood. Since the discovery in 2000 that muscle contraction releases IL-6, the number of exercise-associated signalling molecules that have been identified has multiplied. Exerkines are defined as signalling moieties released in response to acute and/or chronic exercise, which exert their effects through endocrine, paracrine and/or autocrine pathways. A multitude of organs, cells and tissues release these factors, including skeletal muscle (myokines), the heart (cardiokines), liver (hepatokines), white adipose tissue (adipokines), brown adipose tissue (baptokines) and neurons (neurokines). Exerkines have potential roles in improving cardiovascular, metabolic, immune and neurological health. As such, exerkines have potential for the treatment of cardiovascular disease, type 2 diabetes mellitus and obesity, and possibly in the facilitation of healthy ageing. This Review summarizes the importance and current state of exerkine research, prevailing challenges and future directions.
Objective: Our primary objective was to examine the associations of the Mediterranean (MED), the Dietary Approaches to Stop Hypertension (DASH), and the Alternate Healthy Eating Index (AHEI) diet ...with total mortality. Our secondary objective was to examine the association of these three dietary patterns with cardiovascular disease (CVD) and cancer mortality. Research: Design and Methods: We prospectively studied 15,768 men from the Physicians’ Health Study who completed a semi-quantitative food-frequency questionnaire. Scores from each dietary pattern were divided into quintiles. Multivariable Cox regression models were used to estimate hazard ratio’s (95% confidence intervals) of mortality. Results: At baseline, average age was 65.9 ± 8.9 years. There were 1763 deaths, including 488 CVD deaths and 589 cancer deaths. All diet scores were inversely associated with risk for all-cause mortality: Hazard ratios (95% CI) of all-cause mortality from lowest to highest quintile for MED diet were 1.0 (reference), 0.85 (0.73–0.98), 0.80 (0.69–0.93), 0.77 (0.66–0.90), and 0.68 (0.58–0.79); corresponding values were 1.0 (reference), 0.96 (0.82–1.12), 0.95 (0.82–1.11), 0.88 (0.75–1.04), and 0.83 (0.71–0.99) for DASH diet and 1.0 (reference), 0.88 (0.77–1.02), 0.82 (0.71–0.95), 0.69 (0.59, 0.81), and 0.56 (0.47–0.67) for AHEI diet, after adjusting for age, energy, smoking, exercise, BMI, hypertension, coronary heart disease, congestive heart failure, diabetes, and atrial fibrillation. For cause-specific mortality, MED and AHEI scores were inversely associated with lower risk for CVD mortality, whereas AHEI and MED scores were inversely associated with lower risk for cancer mortality. Conclusion: Within this cohort of male physicians, AHEI, MED, and DASH scores were each inversely associated with mortality from all causes.
Physical activity and its sustained and purposeful performance-exercise-promote a broad and diverse set of metabolic and cardiovascular health benefits. Regular exercise is the most effective way to ...improve cardiorespiratory fitness, a measure of one's global cardiovascular, pulmonary and metabolic health, and one of the strongest predictors of future health risk. Here, we describe how exercise affects individual organ systems related to cardiometabolic health, including the promotion of insulin and glucose homeostasis through improved efficiency in skeletal muscle glucose utilization and enhanced insulin sensitivity; beneficial changes in body composition and adiposity; and improved cardiac mechanics and vascular health. We subsequently identify knowledge gaps that remain in exercise science, including heterogeneity in exercise responsiveness. While the application of molecular profiling technologies in exercise science has begun to illuminate the biochemical pathways that govern exercise-induced health promotion, much of this work has focused on individual organ systems and applied single platforms. New insights into exercise-induced secreted small molecules and proteins that impart their effects in distant organs ("exerkines") highlight the need for an integrated approach towards the study of exercise and its global effects; efforts that are ongoing.
Physical activity (PA) and exercise are widely recognized as essential components of primary and secondary cardiovascular disease (CVD) prevention efforts and are emphasized in the health promotion ...guidelines of numerous professional societies and committees. The protean benefits of PA and exercise extend across the spectrum of CVD, and include the improvement and reduction of risk factors and events for atherosclerotic CVD (ASCVD), cardiometabolic disease, heart failure, and atrial fibrillation (AF), respectively. Here, we highlight recent insights into the salutary effects of PA and exercise on the primary and secondary prevention of ASCVD, including their beneficial effects on both traditional and nontraditional risk mediators; exercise "prescriptions" for ASCVD; the role of PA regular exercise in the prevention and treatment of heart failure; and the relationships between, PA, exercise, and AF. While our understanding of the relationship between exercise and CVD has evolved considerably, several key questions remain including the association between extreme volumes of exercise and subclinical ASCVD and its risk; high-intensity exercise and resistance (strength) training as complementary modalities to continuous aerobic exercise; and dose- and intensity-dependent associations between exercise and AF. Recent advances in molecular profiling technologies (ie, genomics, transcriptomics, proteomics, and metabolomics) have begun to shed light on interindividual variation in cardiometabolic responses to PA and exercise and may provide new opportunities for clinical prediction in addition to mechanistic insights.
Regular exercise has many favorable effects on human health, which may be mediated in part by the release of circulating bioactive factors during each bout of exercise. Limited data exist regarding ...the kinetic responses of plasma proteins during and after acute exercise. Proteomic profiling of 4163 proteins was performed using a large-scale, affinity-based platform in 75 middle-aged adults who were referred for treadmill exercise stress testing. Plasma proteins were quantified at baseline, peak exercise, and 1-h postexercise, and those with significant changes at both exercise timepoints were further examined for their associations with cardiometabolic traits and change with aerobic exercise training in the Health, Risk Factors, Exercise Training and Genetics Family Study, a 20-week exercise intervention study. A total of 765 proteins changed (false discovery rate < 0.05) at peak exercise compared to baseline, and 128 proteins changed (false discovery rate < 0.05) at 1-h postexercise. The 56 proteins that changed at both timepoints included midkine, brain-derived neurotrophic factor, metalloproteinase inhibitor 4, and coiled-coil domain-containing protein 126 and were enriched for secreted proteins. The majority had concordant direction of change at both timepoints. Across all proteins assayed, gene set enrichment analysis showed increased abundance of coagulation-related proteins at 1-h postexercise. Forty-five proteins were associated with at least one measure of adiposity, lipids, glucose homeostasis, or cardiorespiratory fitness in Health, Risk Factors, Exercise Training and Genetics Family Study, and 20 proteins changed with aerobic exercise training. We identified hundreds of novel proteins that change during acute exercise, most of which resolved by 1 h into recovery. Proteins with sustained changes during exercise and recovery may be of particular interest as circulating biomarkers and pathways for further investigation in cardiometabolic diseases. These data will contribute to a biochemical roadmap of acute exercise that will be publicly available for the entire scientific community.
Display omitted
•Profiled 4163 plasma proteins at rest, peak exercise, and 1-h after exercise.•Identified large proteomic perturbations at peak exercise that resolve 1-h later.•Observed increased coagulation-related proteins post exercise but not at peak.•Proteins with sustained changes were related to cardiometabolic traits.
After measuring 4163 circulating proteins before, during, and 1-h after treadmill exercise in 75 middle-aged adults, we found that 765 proteins changed at peak exercise, and the majority of these proteins returned to baseline abundance 1-h after. Of 56 proteins with sustained change at peak exercise and after rest, there was enrichment for known secreted proteins and association with cardiometabolic traits in an independent cohort, suggesting that these proteins may be promising candidates for further investigation.
The aim of the HERITAGE Family Study was to investigate individual differences in response to a standardized endurance exercise program, the role of familial aggregation, and the genetics of response ...levels of cardiorespiratory fitness and cardiovascular disease and diabetes risk factors. Here we summarize the findings and their potential implications for cardiometabolic health and cardiorespiratory fitness. It begins with overviews of background and planning, recruitment, testing and exercise program protocol, quality control measures, and other relevant organizational issues. A summary of findings is then provided on cardiorespiratory fitness, exercise hemodynamics, insulin and glucose metabolism, lipid and lipoprotein profiles, adiposity and abdominal visceral fat, blood levels of steroids and other hormones, markers of oxidative stress, skeletal muscle morphology and metabolic indicators, and resting metabolic rate. These summaries document the extent of the individual differences in response to a standardized and fully monitored endurance exercise program and document the importance of familial aggregation and heritability level for exercise response traits. Findings from genomic markers, muscle gene expression studies, and proteomic and metabolomics explorations are reviewed, along with lessons learned from a bioinformatics-driven analysis pipeline. The new opportunities being pursued in integrative -omics and physiology have extended considerably the expected life of HERITAGE and are being discussed in relation to the original conceptual model of the study.
Despite good adherence to supervised endurance exercise training (EET), some individuals experience no or little improvement in peripheral insulin sensitivity. The genetic and molecular mechanisms ...underlying this phenomenon are currently not understood. By investigating genome-wide variants associated with baseline and exercise-induced changes (∆) in insulin sensitivity index (S
) in healthy volunteers, we have identified novel candidate genes whose mouse knockouts phenotypes were consistent with a causative effect on S
. An integrative analysis of functional genomic and transcriptomic profiles suggests genetic variants have an aggregate effect on baseline S
and ∆S
, focused around cholinergic signalling, including downstream calcium and chemokine signalling. The identification of calcium regulated MEF2A transcription factor as the most statistically significant candidate driving the transcriptional signature associated to ∆S
further strengthens the relevance of calcium signalling in EET mediated S
response.
PDF
