Predicting the responsiveness to regular exercise is a topic of great relevance due to its potential role in personalized exercise medicine applications. The present review focuses on ...cardiorespiratory fitness (commonly measured by maximal oxygen uptake, V̇O2 max ), a trait with wide‐ranging impact on health and performance indicators. Gains in V̇O2 max demonstrate large inter‐individual variation even in response to standardized exercise training programmes. The estimated ΔVO2 max heritability of 47% suggests that genomic‐based predictors alone are insufficient to account for the total trainability variance. Candidate gene and genome‐wide linkage studies have not significantly contributed to our understanding of the molecular basis of trainability. A genome‐wide association study suggested that V̇O2 max trainability is influenced by multiple genes of small effects, but these findings still await rigorous replication. Valuable evidence, however, has been obtained by combining skeletal muscle transcript abundance profiles with common DNA variants for the prediction of the V̇O2 max response to exercise training. Although the physiological determinants of V̇O2 max measured at a given time are largely enunciated, what is poorly understood are the details of tissue‐specific molecular mechanisms that limit V̇O2 max and related signalling pathways in response to exercise training. Bioinformatics explorations based on thousands of variants have been used to interrogate pathways and systems instead of single variants and genes, and the main findings, along with those from exercise experimental studies, have been summarized here in a working model of V̇O2 max trainability.
A working model of the two basic components of research focused on the trainability of V̇O2 max . The first component aims at identifying biomarkers and predictors of variation in responsiveness. The second targets technologies, research strategies and designs that have the potential to shed light on the physiology, pathways, systems, signalling, and small and large molecular transducers of adaptability to regular exercise with an emphasis on individual differences. See text for more details.
Proteins are effector molecules that mediate the functions of genes
and modulate comorbidities
, behaviors and drug treatments
. They represent an enormous potential resource for personalized, ...systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11 different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85 million protein measurements in 16,894 participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning
coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.
There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory ...fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability.In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels-a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability.
Individuals differ in the response to regular exercise. Whether there are people who experience adverse changes in cardiovascular and diabetes risk factors has never been addressed.
An adverse ...response is defined as an exercise-induced change that worsens a risk factor beyond measurement error and expected day-to-day variation. Sixty subjects were measured three times over a period of three weeks, and variation in resting systolic blood pressure (SBP) and in fasting plasma HDL-cholesterol (HDL-C), triglycerides (TG), and insulin (FI) was quantified. The technical error (TE) defined as the within-subject standard deviation derived from these measurements was computed. An adverse response for a given risk factor was defined as a change that was at least two TEs away from no change but in an adverse direction. Thus an adverse response was recorded if an increase reached 10 mm Hg or more for SBP, 0.42 mmol/L or more for TG, or 24 pmol/L or more for FI or if a decrease reached 0.12 mmol/L or more for HDL-C. Completers from six exercise studies were used in the present analysis: Whites (N = 473) and Blacks (N = 250) from the HERITAGE Family Study; Whites and Blacks from DREW (N = 326), from INFLAME (N = 70), and from STRRIDE (N = 303); and Whites from a University of Maryland cohort (N = 160) and from a University of Jyvaskyla study (N = 105), for a total of 1,687 men and women. Using the above definitions, 126 subjects (8.4%) had an adverse change in FI. Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C. About 7% of participants experienced adverse responses in two or more risk factors.
Adverse responses to regular exercise in cardiovascular and diabetes risk factors occur. Identifying the predictors of such unwarranted responses and how to prevent them will provide the foundation for personalized exercise prescription.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Effects of exercise on HDL functionality Ruiz-Ramie, Jonathan J; Barber, Jacob L; Sarzynski, Mark A
Current opinion in lipidology,
02/2019, Letnik:
30, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Low HDL-cholesterol (HDL-C) levels are a strong predictor of cardiovascular disease risk and can be improved with regular exercise. However, raising HDL-C levels pharmacologically has not shown ...convincing clinical benefits. Thus, research has recently focused on identifying therapies that improve HDL function, with exercise representing such a potential therapy. The purpose of this review is to summarize the effects of exercise interventions on HDL function.
The effects of exercise and lifestyle interventions on the primary atheroprotective functions of HDL are reviewed, namely, cholesterol efflux, antioxidative, and anti-inflammatory properties. Differences in study design, study population, and assays are discussed to aid in the interpretation of the reviewed studies.
There is mixed evidence that regular aerobic exercise improves cholesterol efflux capacity, with recent research suggesting an exercise dose threshold needs to be exceeded to produce beneficial effects. There is preliminary evidence that exercise improves the antioxidative and anti-inflammatory properties of HDL. Although exercise represents a potential therapeutic approach to improve HDL function, the heterogeneity and/or lack of findings warrants more and larger studies to determine what HDL function(s) are most responsive to regular exercise and what dose of exercise elicits the greatest improvements in HDL functionality.
Clustering of obesity, coronary artery disease, and cardiovascular disease risk factors is observed in epidemiological studies and clinical settings. Twin and family studies have provided some ...supporting evidence for the clustering hypothesis. Loci nearest a lead single nucleotide polymorphism (SNP) showing genome-wide significant associations with coronary artery disease, body mass index, C-reactive protein, blood pressure, lipids, and type 2 diabetes mellitus were selected for pathway and network analyses. Eighty-seven autosomal regions (181 SNPs), mapping to 56 genes, were found to be pleiotropic. Most pleiotropic regions contained genes associated with coronary artery disease and plasma lipids, whereas some exhibited coaggregation between obesity and cardiovascular disease risk factors. We observed enrichment for liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor/RXR nuclear receptor signaling among pleiotropic genes and for signatures of coronary artery disease and hepatic steatosis. In the search for functionally interacting networks, we found that 43 pleiotropic genes were interacting in a network with an additional 24 linker genes. ENCODE (Encyclopedia of DNA Elements) data were queried for distribution of pleiotropic SNPs among regulatory elements and coding sequence variations. Of the 181 SNPs, 136 were annotated to ≥1 regulatory feature. An enrichment analysis found over-representation of enhancers and DNAse hypersensitive regions when compared against all SNPs of the 1000 Genomes pilot project. In summary, there are genomic regions exerting pleiotropic effects on cardiovascular disease risk factors, although only a few included obesity. Further studies are needed to resolve the clustering in terms of DNA variants, genes, pathways, and actionable targets.
Low cardiorespiratory fitness is a powerful predictor of morbidity and cardiovascular mortality. In 473 sedentary adults, all whites, from 99 families of the Health, Risk Factors, Exercise Training, ...and Genetics (HERITAGE) Family Study, the heritability of gains in maximal O(2) uptake (VO(2max)) after exposure to a standardized 20-wk exercise program was estimated at 47%. A genome-wide association study based on 324,611 single-nucleotide polymorphisms (SNPs) was undertaken to identify SNPs associated with improvements in VO(2max) Based on single-SNP analysis, 39 SNPs were associated with the gains with P < 1.5 × 10(-4). Stepwise multiple regression analysis of the 39 SNPs identified a panel of 21 SNPs that accounted for 49% of the variance in VO(2max) trainability. Subjects who carried ≤9 favorable alleles at these 21 SNPs improved their VO(2max) by 221 ml/min, whereas those who carried ≥19 of these alleles gained, on average, 604 ml/min. The strongest association was with rs6552828, located in the acyl-CoA synthase long-chain member 1 (ACSL1) gene, which accounted by itself for ~6% of the training response of VO(2max). The genes nearest to the SNPs that were the strongest predictors were PR domain-containing 1 with ZNF domain (PRDM1); glutamate receptor, ionotropic, N-methyl-D-aspartate 3A (GRIN3A); K(+) channel, voltage gated, subfamily H, member 8 (KCNH8); and zinc finger protein of the cerebellum 4 (ZIC4). The association with the SNP nearest to ZIC4 was replicated in 40- to 65-yr-old, sedentary, overweight, and dyslipidemic subjects trained in Studies of a Targeted Risk Reduction Intervention Through Defined Exercise (STRRIDE; n = 183). Two SNPs were replicated in sedentary obese white women exercise trained in the Dose Response to Exercise (DREW) study (n = 112): rs1956197 near dishevelled associated activator of morphogenesis 1 (DAAM1) and rs17117533 in the vicinity of necdin (NDN). The association of SNPs rs884736 in the calmodulin-binding transcription activator 1 (CAMTA1) locus and rs17581162 ~68 kb upstream from regulator of G protein signaling 18 (RGS18) with the gains in VO(2max) in HERITAGE whites were replicated in HERITAGE blacks (n = 247). These genomic predictors of the response of Vo(2max) to regular exercise provide new targets for the study of the biology of fitness and its adaptation to regular exercise. Large-scale replication studies are warranted.
Overweight and obesity (OWOB) is a global epidemic. Adults and adolescents from low-income households are at higher risk to be OWOB. This study examined the relationship between income and OWOB ...prevalence in children and adolescents (518 years) in the United States (US) within and across race/ethnicities, and changes in this relationship from 1971 to 2014.
A meta-analysis of a nationally representative sample (N = 73,891) of US children and adolescents drawn from three datasets (i.e., National Health and Nutrition Examination Survey, National Longitudinal Survey of Youth, & the Early Childhood Longitudinal Program) which included 14 cross-sectional waves spanning 1971-2014 was conducted. The exposure was household income-to-poverty ratio (low income = 0.00-1.00, middle income = 1.01-4.00, high income >4.00) with prevalence of overweight or obesity (body mass index ≥ 85th percentile) as the outcome.
Children and adolescents from middle-income and high-income households were 0.78 (95% CI = 0.72, 0.83) and 0.68 (95% CI = 0.59, 0.77) times as likely to be OWOB compared to children and adolescents in low-income households. Separate analyses restricted to each racial/ethnic group showed children and adolescents from middle- and high-income households were less likely to be OWOB compared to their low-income peers within the White, Hispanic, and Other race/ethnic groups. Children and adolescents from low-income households who were Black were not more likely to be OWOB than their high- and middle-income counterparts. Analyses within each income stratum indicated that race/ethnicity was not related to the prevalence of OWOB in low-income households. However, racial/ethnic differences in OWOB were evident for children and adolescents in middle- and high-income households. Disparities in the prevalence of OWOB between low-income children and adolescents and their middle- and high-income counterparts have increased from 1971 to 2014.
Income and OWOB are related in US children and adolescents. Racial/ethnic differences in the prevalence of OWOB emerge in middle- and high-income households. Disparities in OWOB prevalence are growing.
There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained ...endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE—Measures of HDL (high-density lipoprotein) function are associated with cardiovascular disease. However, the effects of regular exercise on these measures is largely unknown. Thus, we ...examined the effects of different doses of exercise on 3 measures of HDL function in 2 randomized clinical exercise trials.
APPROACH AND RESULTS—Radiolabeled and boron dipyrromethene difluoride–labeled cholesterol efflux capacity and HDL-apoA-I (apolipoprotein A-I) exchange were assessed before and after 6 months of exercise training in 2 cohortsSTRRIDE-PD (Studies of Targeted Risk Reduction Interventions through Defined Exercise, in individuals with Pre-Diabetes; n=106) and E-MECHANIC (Examination of Mechanisms of exercise-induced weight compensation; n=90). STRRIDE-PD participants completed 1 of 4 exercise interventions differing in amount and intensity. E-MECHANIC participants were randomized into 1 of 2 exercise groups (8 or 20 kcal/kg per week) or a control group. HDL-C significantly increased in the high-amount/vigorous-intensity group (3±5 mg/dL; P=0.02) of STRRIDE-PD, whereas no changes in HDL-C were observed in E-MECHANIC. In STRRIDE-PD, global radiolabeled efflux capacity significantly increased 6.2% (SEM, 0.06) in the high-amount/vigorous-intensity group compared with all other STRRIDE-PD groups (range, −2.4 to −8.4%; SEM, 0.06). In E-MECHANIC, non-ABCA1 (ATP-binding cassette transporter A1) radiolabeled efflux significantly increased 5.7% (95% CI, 1.2–10.2%) in the 20 kcal/kg per week group compared with the control group, with no change in the 8 kcal/kg per week group (2.6%; 95% CI, −1.4 to 6.7%). This association was attenuated when adjusting for change in HDL-C. Exercise training did not affect BODIPY-labeled cholesterol efflux capacity or HDL-apoA-I exchange in either study.
CONCLUSIONS—Regular prolonged vigorous exercise improves some but not all measures of HDL function. Future studies are warranted to investigate whether the effects of exercise on cardiovascular disease are mediated in part by improving HDL function.
CLINICAL TRIAL REGISTRATION—URLhttps://www.clinicaltrials.gov. Unique identifiersNCT00962962 and NCT01264406.
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