Long-term Leisure-time Physical Activity and Serum Metabolome

Abstract

Background-Long-term physical inactivity seems to cause many health problems. We studied whether persistent physical activity compared with inactivity has a global effect on serum metabolome toward reduced cardiometabolic disease risk. Methods and Results-Sixteen same-sex twin pairs (mean age, 60 years) were selected from a cohort of twin pairs on the basis of their >30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in 3 populationbased cohorts (mean ages, 31-52 years) were also studied (1037 age-and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance spectroscopy. We used permutation analysis to estimate the significance of the multivariate effect combined across all metabolic measures; univariate effects were estimated by paired testing in twins and in matched pairs in the cohorts, and by meta-analysis over all substudies. Persistent physical activity was associated with the multivariate metabolic profile in the twins (P=0.003), and a similar pattern was observed in all 3 population cohorts with differing mean ages. Isoleucine, α1-acid glycoprotein, and glucose were lower in the physically active than in the inactive individuals (P<0.001 in meta-analysis); serum fatty acid composition was shifted toward a less saturated profile; and lipoprotein subclasses were shifted toward lower very-low-density lipoprotein (P<0.001) and higher large and very large high-density lipoprotein (P<0.001) particle concentrations. The findings persisted after adjustment for body mass index. Conclusions-The numerous differences found between persistently physically active and inactive individuals in the circulating metabolome together indicate better metabolic health in the physically active than in inactive individuals. T he modern environment is conducive to a sedentary lifestyle with an increased propensity for obesity and adverse cardiometabolic risk. The current obesity epidemic is ultimately due to an imbalance between energy intake and energy expenditure.1 High leisure-time physical activity and high levels of physical fitness are associated with reduced levels of total and visceral fat; decreased cardiometabolic risk factors; reduced prevalence of metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease; and reduced mortality. 2 Editorial see p 317 Clinical Perspective on p 348Research on the specific effects of long-term physical activity is challenging because of the considerable difficulties in conducting randomized, controlled, long-term exercise trials. We combined 2 population-based approaches to address this issue. To control for childhood environments and partially for genetic factors possibly underlying the associations between physical activity and cardiometabolic risk factor levels, we selected same-sex twin pairs from a population-based cohort of baseline-healthy twin pairs 3,4 on the basis of their 32-year discordance for physical activity. To test our findings in the general population, we identified persistently active o...

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“…[12] Gene expression in adipose tissue and in skeletal muscle was quantified by nuclear magnetic resonance spectroscopy to yield the metabolome. The altered gene expression in the muscle of the active twins was associated with increased fatty acid oxidation, while in adipose tissue, fatty acid storage was decreased (Fig.…”

“…Circulating metabolites LDL-C HDL-C Superior metabolic protection For detailed proposals refer to Kujala et al [12] Note, the beneficially decreased serum lowdensity lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) levels.…”

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“…While expanding the body of evidence linking BCAAs to cardiometabolic health, the data provided by Kujala and colleagues 9 offer clues regarding the extent to which BCAAs may be pathobiological markers, mediators, or both. In addition to the main analyses, they collected adipose and muscle tissue samples from 10 of the studied twin pairs and identified gene sets that were upregulated in active compared with inactive twins.…”

“…15 Interestingly, experimental studies indicate that circulating amino acids can induce mitochondrial biogenesis to promote amino acid catabolism, in which BCAA oxidation enzymes residing in adipose and muscle tissue respond to increased BCAA concentrations that result from exercise-stimulated protein breakdown. 16 Accordingly, nodes that represent gene expression for BCAA degradation are part of the network proposed by Kujala and colleagues, 9 and variations in BCAA as well as other amino acids are linked most closely to measures of adiposity.…”

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“…Bliksrud nevner uten naermere spesifisering at immobilisering gir omfattende metabolske endringer og henviser til en studie av ettbeins fiksering og etterfølgende mRNA-analyser i muskelbiopsier. Det finnes mer relevante og sammenlignbare studier av serummetabolitter ved immobilisering, der funnene ikke sammenfaller med det vi fant pasientene med kronisk utmattelsessyndrom (7,8).…”