Tuija Leskinen

Long-term Leisure-time Physical Activity and Serum Metabolome

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 population-based 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, &agr;1-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.

Leisure-time physical activity and high-risk fat: a longitudinal population-based twin study

Background and Objective:Exercise is thought to reduce high-risk body fat, but intervention studies are frequently limited by short follow-ups and observational studies by genetic selection. Therefore, we studied the effects of a physically inactive vs active lifestyle on high-risk (visceral, liver and intramuscular) fat in twin pairs discordant for leisure-time physical activity habits for over 30 years.Design:A longitudinal population-based twin study.Subjects:Sixteen middle-aged (50–74 years) same-sex twin pairs (seven monozygotic (MZ), nine dizygotic (DZ)) with long-term discordance for physical activity habits were comprehensively identified from the Finnish Twin Cohort (TWINACTIVE study). Discordance was initially defined in 1975 and the same co-twin remained significantly more active during the 32-year-long follow-up.Main Outcome Measures:Magnetic resonance imaging-assessed visceral, liver and intramuscular fat.Results:In within-pair analyses carried out after the adult life-long discordance in physical activity habits, the physically inactive co-twins had 50% greater visceral fat area compared with the active co-twins (mean difference 55.5 cm2, 95% confidence interval (CI) 7.0–104.1, P=0.010). The liver fat score was 170% higher (13.2, 95% CI 3.5–22.8, P=0.030) and the intramuscular fat area 54% higher (4.9 cm2, 95% CI 1.9–7.9, P=0.002) among the inactive co-twins. All the trends were similar for MZ and DZ pairs. Peak oxygen uptake was inversely associated with visceral (r=−0.46, P=0.012) and intramuscular fat area (r=−0.48, P=0.028), with similar trends in intrapair difference correlations (r=−0.57, P=0.021 and r=−0.50, P=0.056, respectively). The intrapair difference correlation between visceral and intramuscular fat was also high (r=0.65, P=0.009).Conclusion:Regular physical activity seems to be an important factor in preventing the accumulation of high-risk fat over time, even after controlling for genetic liability and childhood environment. Therefore, the prevention and treatment of obesity should emphasize the role of regular leisure-time physical activity.

Differences in Muscle and Adipose Tissue Gene Expression and Cardio-Metabolic Risk Factors in the Members of Physical Activity Discordant Twin Pairs

High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50–74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing active vs. inactive co-twin gene expression ratios. Our findings showed that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in the muscle tissue samples was chronically up-regulated for the central pathways related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. Up-regulation of these pathways was associated in particular with aerobic fitness and high HDL cholesterol levels. In fat tissue we found physical activity-associated increases in the expression of polyunsaturated fatty acid metabolism and branched-chain amino acid degradation gene sets both of which associated with decreased ‘high-risk’ ectopic body fat and plasma glucose levels. Consistent with other findings, plasma lipidomics analysis showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. Our findings identified skeletal muscle and fat tissue pathways which are associated with the long-term physical activity and reduced cardio-metabolic disease risk, including increased aerobic fitness. In particular, improved skeletal muscle oxidative energy and lipid metabolism as well as changes in adipocyte function and redistribution of body fat are associated with reduced cardio-metabolic risk.

Effects of 32-Year Leisure Time Physical Activity Discordance in Twin Pairs on Health (TWINACTIVE Study): Aims, Design and Results for Physical Fitness

The physically active lifestyle is associated with low future morbidity and mortality, but the causality between physical activity and health is not always clear. As some inherited biological characteristics and childhood experiences may cause selection bias in observational studies, we sought to take them into account by identifying 16 twin pairs (7 MZ, 9 DZ, mean age 60 years) discordant for leisure time physical activity habits for thirty years. We conducted detailed health-related examinations among these twin pairs. Our main aims were to study the effects of physical activity and genes on fitness and body composition, with special reference to body fat compartments, metabolic syndrome components and related diseases and risk factor levels, status of arteries, structure and function of the heart, bone properties, and muscle and fat tissue-related mechanisms linked to physical activity and chronic disease development. Our physical activity assessments showed that inactive co-twins were on average 8.8 MET hours/day less active than their active co-twins through out their midlife (2.2+/-2.3 vs. 11.0+/-4.1 MET h/day, p< .001). Follow-up fitness tests showed that physically inactive co-twins were less fit than their active co-twins (estimated VO(2peak) 26.4+/-4.9 vs. 32.5+/-5.5 ml/kg/min, p< .001). Similar differences were found in both MZ and DZ pairs. On the basis of earlier epidemiological observations on nonrelated individuals, these physical activity and fitness differences are large enough to cause differences in many mechanisms and risk factors related to the development of chronic diseases and to permit future analyses.

Associations of physical activity, fitness, and body composition with heart rate variability based indicators of stress and recovery on workdays: a cross-sectional study

BackgroundThe purpose of this study was to investigate how physical activity (PA), cardiorespiratory fitness (CRF), and body composition are associated with heart rate variability (HRV)-based indicators of stress and recovery on workdays. Additionally, we evaluated the association of objectively measured stress with self-reported burnout symptoms.MethodsParticipants of this cross-sectional study were 81 healthy males (age range 26–40 y). Stress and recovery on workdays were measured objectively based on HRV recordings. CRF and anthropometry were assessed in laboratory conditions. The level of PA was based on a detailed PA interview (MET index [MET-h/d]) and self-reported activity class.ResultsPA, CRF, and body composition were significantly associated with levels of stress and recovery on workdays. MET index (P < 0.001), activity class (P = 0.001), and CRF (P = 0.019) were negatively associated with stress during working hours whereas body fat percentage (P = 0.005) was positively associated. Overall, 27.5% of the variance of total stress on workdays (P = 0.001) was accounted for by PA, CRF, and body composition. Body fat percentage and body mass index were negatively associated with night-time recovery whereas CRF was positively associated. Objective work stress was associated (P = 0.003) with subjective burnout symptoms.ConclusionsPA, CRF, and body composition are associated with HRV-based stress and recovery levels, which needs to be taken into account in the measurement, prevention, and treatment of work-related stress. The HRV-based method used to determine work-related stress and recovery was associated with self-reported burnout symptoms, but more research on the clinical importance of the methodology is needed.

Physical Activity, Fitness, Glucose Homeostasis, and Brain Morphology in Twins

PURPOSE The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. METHODS From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. RESULTS According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P < 0.001. CONCLUSIONS Among healthy adult male twins in their mid-30s, a greater level of physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

Leisure-time physical activity and nutrition: a twin study.

OBJECTIVE To determine the association between long-term leisure-time physical activity/inactivity and eating behaviours in twin pairs discordant for physical activity for 30 years. DESIGN Co-twin control design with cross-sectional data collection using questionnaire on eating habits and 5 d food diary. Differences in eating behaviours between physically active and inactive co-twins were analysed with pairwise tests. SETTING Finland. SUBJECTS Sixteen same-sex twin pairs (seven monozygotic and nine dizygotic, mean age 60 years) discordant for physical activity, selected from the Finnish Twin Cohort on the basis of physical activity discordance for 30 years, blinded to their possible differences in eating behaviours. RESULTS The eating habits questionnaire revealed that physically active co-twins more frequently reported that it is easy to eat according to need, whereas overeating and/or restrictive eating was more common among the inactive co-twins (P = 0·035). Avoiding calories was more common among the active than inactive co-twins (P = 0·034). Based on food diaries the physically active co-twins had daily energy intake on average 15·5 kJ/kg higher than their inactive co-twins (P = 0·030). The active co-twins also had a higher intake of vitamin C (P = 0·004), total water (P = 0·044), legumes and nuts (P = 0·015) and sweets (P = 0·036), as well as a lower energy-adjusted intake of meat (P = 0·013). CONCLUSIONS The physically active persons seem to eat more but not necessarily healthier food. However, habitual physical activity may help in eating according to need and in reaching and maintaining a healthy body composition. Therefore, it is necessary to incorporate both dietary and physical activity advice into health counselling.

Right ventricular metabolic adaptations to high-intensity interval and moderate-intensity continuous training in healthy middle-aged men.

Despite the recent studies on structural and functional adaptations of the right ventricle (RV) to exercise training, adaptations of its metabolism remain unknown. We investigated the effects of short-term, high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on RV glucose and fat metabolism. Twenty-eight untrained, healthy 40-55 yr-old-men were randomized into HIIT (n = 14) and MICT (n = 14) groups. Subjects performed six supervised cycle ergometer training sessions within 2 wk (HIIT session: 4-6 × 30 s all-out cycling/4-min recovery; MICT session: 40-60 min at 60% peak O2 uptake). Primary outcomes were insulin-stimulated RV glucose uptake (RVGU) and fasted state RV free fatty acid uptake (RVFFAU) measured by positron emission tomography. Secondary outcomes were changes in RV structure and function, determined by cardiac magnetic resonance. RVGU decreased after training (-22% HIIT, -12% MICT, P = 0.002 for training effect), but RVFFAU was not affected by the training (P = 0.74). RV end-diastolic and end-systolic volumes, respectively, increased +5 and +7% for HIIT and +4 and +8% for MICT (P = 0.002 and 0.005 for training effects, respectively), but ejection fraction mildly decreased (-2% HIIT, -4% MICT, P = 0.034 for training effect). RV mass and stroke volume remained unaltered. None of the observed changes differed between the training groups (P > 0.12 for group × training interaction). Only 2 wk of physical training in previously sedentary subjects induce changes in RV glucose metabolism, volumes, and ejection fraction, which precede exercise-induced hypertrophy of RV.

Different predictors of right and left ventricular metabolism in healthy middle-aged men

Dysfunction of the right ventricle (RV) plays a crucial role in the outcome of various cardiovascular diseases. Previous studies on RV metabolism are sparse although evidence implies it may differ from left ventricular (LV) metabolism. Therefore, the aims of this study were (1) to determine predictors of RV glucose uptake (GU) and free fatty acid uptake (FFAU) and (2) to compare them to predictors of LV metabolism in healthy middle-aged men. Altogether 28 healthy, sedentary, middle-aged (40–55 years) men were studied. Insulin-stimulated GU and fasting FFAU were measured by positron emission tomography and RV and LV structural and functional parameters by cardiac magnetic resonance. Several parameters related to whole-body health were also measured. Predictors of RV and LV metabolism were determined by pairwise correlation analysis, lasso regression models, and variable clustering using heatmap. RVGU was most strongly predicted by age and moderately by RV ejection fraction (EF). The strongest determinants of RVFFAU were exercise capacity (peak oxygen uptake), resting heart rate, LVEF, and whole-body insulin-stimulated glucose uptake rate. When considering LV metabolism, age and RVEF were associated also with LVGU. In addition, LVGU was strongly, and negatively, influenced by whole-body insulin-stimulated glucose uptake rate. LVFFAU was predicted only by LVEF. This study shows that while RV and LV metabolism have shared characteristics, they also have unique properties. Age of the subject should be taken into account when measuring myocardial glucose utilization. Ejection fraction is related to myocardial metabolism, and even so that RVEF may be more closely related to GU of both ventricles and LVEF to FFAU of both ventricles, a finding supporting the ventricular interdependence. However, only RV fatty acid utilization associates with exercise capacity so that better physical fitness in a relatively sedentary population is related with decreased RV fat metabolism. To conclude, this study highlights the need for further study designed specifically on less-known RV, as the results on LV metabolism and physiology may not be directly applicable to the RV.

Health-Related Findings Among Twin Pairs Discordant for Leisure-Time Physical Activity for 32 Years: The TWINACTIVE Study Synopsis.

We are lacking very long-term and controlled intervention studies investigating the effects of habitual physical activity on health-related factors. To address this gap, we performed a natural experiment by identifying same-sex twin pairs in which the co-twins of each pair differed with respect to leisure-time physical-activity habits throughout their adult life. Our criterion for the discordance was that the same co-twin had a higher leisure time-activity volume than that of the other member of the pair at the majority -- if not all -- of the follow-up time points according to reported/interviewed physical-activity data. Overall, we identified and conducted multidimensional health-related measurements (including fitness, body composition, cardiometabolic risk factor levels, bone and arterial status, and exercise motivation) of 16 twin pairs (seven monozygotic (MZ) and nine dizygotic (DZ) pairs, mean age 60 years) who had persistent discordance in leisure-time physical-activity habits over three decades (TWINACTIVE study). In our discordant-pair study design, after adjusting for sequence-level genes, both systemic-level metabolic, and site-specific structural findings differed significantly in the pairwise analysis in MZ pairs only. These findings included intrapair differences in accumulated fat depots and structure of heart, arteries, and bones. In addition, our study revealed intrapair differences in metabolic and regulatory pathways, which may partly explain the mechanistic links between long-term physical activity, phenotypic changes, and decreased risk of cardiometabolic diseases.