Publications

Familial aggregation of stroke volume (SV) and cardiac output (Qc by CO2 rebreathing) at 50 Watts (W) and 60 % of maximal oxygen uptake (V˙O2max) as well as their changes in response to a 20-week endurance exercise training program was assessed in 99 Caucasian families who participated in the HERITAGE Family Study. In order to interpret familial influences independent of effects of age, sex, and body size (indexed by body surface area here), SV and Qc levels were adjusted for these primary parameters prior to genetic analysis within four sex-by-generation groups (the responses to training were additionally adjusted for their baseline values). Maximal heritabilities for baseline SV, Qc, and their changes in response to training during the two stages of submaximal exercise were estimated using a familial correlation model. At 50 W, maximal heritabilities reached 41 % and 42 % for baseline SV and Qc, respectively, and were 29 % and 38 % for the respective responses to training. At 60 % of V˙O2max, maximal heritabilities reached 46 % for baseline SV and Qc, and were 24 % and 30 % for the respective responses to training. Generally there were no meaningful differences between the maximal heritabilities at 50 W and 60 % of V˙O2max. However, the maximal heritabilities for the baseline were slightly higher than the estimates for the changes in response to training. Based upon results arising from these non-obese, non-hypertensive, and sedentary families, we found that SV and Qc at 50 W and 60 % of V˙O2max as well as their changes in response to the 20-week endurance exercise training were moderately heritable. Not only genetic determinants but also familial non-genetic factors might attribute to the observed patterns of familial aggregation of SV and Qc during submaximal exercise in the present study.

—High density lipoprotein (HDL) cholesterol concentrations have been shown to increase with regular endurance exercise and, therefore, can contribute to a lower risk of coronary heart disease in physically active individuals compared with sedentary subjects. Although low HDL cholesterol levels are frequently observed in combination with hypertriglyceridemia, some individuals may be characterized by isolated hypoalphalipoproteinemia, ie, low HDL cholesterol levels in the absence of elevated triglyceride (TG) concentrations. The present study compared the responses of numerous lipoprotein-lipid variables to a 20-week endurance exercise training program in men categorized on the basis of baseline TG and HDL cholesterol concentrations: (1) low TG and high HDL cholesterol (normolipidemia), (2) low TG and low HDL cholesterol (isolated low HDL cholesterol), (3) high TG and high HDL cholesterol (isolated high TGs), and (4) high TGs and low HDL cholesterol (high TG/low HDL cholesterol). A series of physical and metabolic variables was measured before and after the training program in a sample of 200 men enrolled in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. At baseline, men with high TG/low HDL cholesterol had more visceral adipose tissue than did men with isolated low HDL cholesterol and men with normolipidemia. The 0.4% (not significant) exercise-induced increase in HDL cholesterol levels in men with isolated low HDL cholesterol suggests that they did not benefit from the “HDL-raising” effect of exercise. In contrast, men with high TG/low HDL cholesterol showed a significant increase in HDL cholesterol levels (4.9%, P <0.005). Whereas both subgroups of men with elevated TG levels showed reductions in plasma TGs (≈−15.0%, P <0.005), only those with high TG/low HDL cholesterol showed significantly reduced apolipoprotein B levels at the end of the study (−6.0%, P <0.005). Multiple regression analyses revealed that the exercise-induced change in abdominal subcutaneous adipose tissue (10.6%, P <0.01) was the only significant correlate of the increase in plasma HDL cholesterol with training in men with high TG/low HDL cholesterol. Results of the present study suggest that regular endurance exercise training may be particularly helpful in men with low HDL cholesterol, elevated TGs, and abdominal obesity.

The aim of this study was to investigate the relationship between submaximal power output at a heart rate of 170 beats/min (PWC170) assessed from a multistage cycle ergometer test and TNFα (chromosome 6p21.3) gene polymorphism detected by Ncol resulting from a G to A base substitution at position -308. Genetic analysis of restriction fragment length polymorphism was undertaken on 320 individual from 117 families (107 parents and 213 offsprings). PWC170 data were adjusted by regression procedure for the effects of age and sex, and were expressed per kg body weight (PWC170KG) or kg fat free mass (PWC170FFM) derived from body density measurements. Using an association study design with unrelated subjects, individuals who were homozygotes for G at position -308 had significantly higher PWC170KG than those who were heterozygotes for the mutation (12.98 ±4.10 vs 11.00±2.72 kpm/kg, P<0.03), but no difference was found for PWC170FFM(P=0.53). The sib-pair linkage analysis procedure with 80 pairs of adult sibs provided no evidence of linkage between the PWC170 phenotypes and the single base polymorphism in the TNFα gene. These results suggest that TNFα gene variability detected with Ncol may be associated with performance in a submaximal power output test adjusted for body mass. However, no linkage relationship could be detected between the performance phenotype and the TNFα marker locus.

695 In the GENATHLETE case control study, we examined the contribution of two polymorphisms in the gene encoding for the endothelial nitric oxide synthase (NOS3). The hypothesis was that this particular gene, as a result of its key role in the synthesis of NO and its potential influence on endothelial function, may play a role in discriminating elite endurance athletes (EEA) from sedentary controls (SC). The EEA group included 213 Caucasian males recruited on the basis that they had a VO2max > 75ml/kg/min. The SC group comprised 197 unrelated sedentary males who had VO2max values below 50ml/kg/min. PCR technique was used to amplify a microsatellite (CA repeat) containing region in intron 13 and a second fragment in intron 4 including a 27bp repeat in the NOS3 gene, located on chromosome 7q36. No difference between EEA and SC was found in genotype distributions or allelic frequencies for the 27bp repeat. The numbers and p-values from chi-square tests for carrier status of the 162bp and 170bp allele of the CA repeat in intron 13 for EEA and SC are presented in table 1.Table 1: Allele distributions and results from chi-square analysis for the 162bp and the 170bp allele of the CA repeat in the NOS3 gene. Chi-square analysis for the allelic distribution of the CA repeat revealed a significant difference between the two groups (p=0,018).Comparing carriers and non-carriers for the various CA repeat alleles, we found significant differences between SC and EEA, with more SC subjects carrying the 170bp allele and more EEA subjects with the 162bp allele (Table 1). In summary, we found suggestive evidence that the two fragments are associated with EEA and SC status, respectively, and may account for some differences between EEA and SC.

The purposes of this study were to examine (a) the effects of acute exercise on metabolic rate 24 and 48 h postexercise and (b) the interaction of acute exercise and the thermic effect of caffeine on metabolic rate and hormonal changes during the late postexercise recovery period. In six young males, who were regular consumers of caffeine, resting energy expenditure was measured before and after caffeine (5 mg∙kg −1 ) and placebo ingestion under the following conditions: (i) control (e.g., no prior exercise), (ii) 24 h postexercise, and (iii) 48 h postexercise. Blood samples were drawn for plasma glucose, insulin, glycerol, free fatty acids, catecholamines, and thyroid hormones (triiodothyronine, thyroxine, and free thyroxine). Results showed that acute exercise did not exert a detectable effect on resting metabolic rate in the late postexercise recovery period, that is, resting metabolic rate was similar among the conditions of control (1.17 ± 0.12 kcal∙min −1 ), 24 h postexercise (1.16 ± 0.12), and 48 h postexercise (1.16 ± 0.11). Caffeine ingestion increased metabolic rate (~7%), but the thermic effect was not different among the experimental conditions. Plasma insulin and norepinephrine were lower after caffeine ingestion, whereas an increase in plasma free fatty acids was noted. Other hormones and substrates did not change significantly in response to caffeine ingestion. Furthermore, the hormonal and substrate milieu was not significantly different 24 and 48 h postexercise when compared with the control condition. Our results support the view that acute exercise does not alter the resting metabolic rate in the late postexercise recovery period. Moreover, acute exercise does not potentiate the thermic effect of caffeine in the late postexercise recovery in caffeine-tolerant males.Key words: caffeine, resting metabolic rate, acute exercise, hormones, substrates.

Evidence is scarce for an association between treadmill performance and cognitive function in healthy young and middle-aged adults. We assessed the hypothesis that duration on treadmill predicts cognitive function 25 years later. Participants were from the population-based Coronary Artery Risk Development in Young Adults (CARDIA) study, a multi-center study of black and white men and women aged 18-30 at recruitment in 1985-86 (year 0). The main independent variable of interest was baseline symptom-limited maximal treadmill test duration as a measure of treadmill performance potential, including its major subcomponent cardiorespiratory fitness (CRF/TPP). Cognitive functions measured were verbal memory (with the Rey auditory-verbal learning (AVLT)), psychomotor speed (Digit Symbol Substitution Test (DSST)) and executive function (modified Stroop interference test, where lower is better). We analyzed 2444 participants who had y0 treadmill testing and y25 cognitive testing. For each additional SD of treadmill duration (2.8 minutes), the DSST was 2.4 digits correctly substituted higher, the AVLT was 0.36 words recalled higher, and the Stroop test time 1.7 seconds less, after accounting for race, sex, age, highest attained education level and center of clinic visit( Table ). Further adjustment for dietary pattern, physical activity, smoking, BMI, alcohol consumption, glomerular filtration rate, blood pressure, cholesterol and diabetes status yielded similar trends for these cognitive function tests. In conclusion, CRF/TPP predicts cognitive function 25 years later independently of other factors among apparently healthy adults. Prospective estimation of cognitive function by treadmill duration at baseline in minimally and fully adjusted model (see text for details), N=2444. Year 25 Digit Symbol Substitution Test: Digits correctly substituted mean±SD: 70.1±15.9 Year 25 Rey Auditory-Verbal Learning Test: Words correctly recalled mean±SD: 8.3±3.3 Year 25 Stroop Test : Seconds to correctly name colors mean±SD: 43.9±12.8 Slope * SE P Slope * SE P Slope * SE P Year 0 treadmill duration (SD) mean±SD: 10.0±2.8 minutes Minimally adjusted 2.4 0.36 &lt;.0001 0.36 0.08 &lt;.0001 -1.7 0.31 &lt;.0001 Fully adjusted 2.3 0.45 &lt;.0001 0.39 0.08 &lt;.0001 -1.2 0.39 0.001 * “Slope” is the difference in the indicated cognitive function per SD (2.8 minutes) of treadmill duration.

No abstract is provided for this article.

PURPOSE The purpose of this abstract was to determine if supplemental estrogen and exercise affected visceral fat levels in postmenopausal women. METHODS Forty-eight healthy and previously sedentary postmenopausal women (mean age = 54.3 yrs) who were enrolled in the HERITAGE Family Study underwent 20 weeks of exercise training. Of these 48 women, 18 were currently taking estrogen replacement without progesterone (ER) and the remaining 30 were taking no hormone supplementation. CT scans were used to measure abdominal visceral fat (AVF) as well as total abdominal fat (TAF) and abdominal subcutaneous fat (ASF). Body mass index (BMI) and waist-to-hip ratios (WHR) were calculated and body fat percentage (%FAT) was assessed using underwater weighing. RESULTS Results showed AVF to be an average of 31.3 cm2 less in the women receiving ER (p < .05). After adjustment for race, this difference remained but statistical significance was borderline (p = .06), as black women had an average of 33.6 cm2 more AVF at baseline than did whites. Mean values for TAF and ASF were also less in the women receiving ER, but did not achieve statistical significance. No differences were found in BMI or %fat, but mean WHR was 5% smaller in the ER group (p < .05). There were no differences in training responses in any of the body composition variables between those taking and those not taking ER. CONCLUSIONS It was concluded that taking supplemental estrogen was associated with lower values of AVF in postmenopausal women and that body composition and fat distribution responses to endurance exercise training did not differ with respect to ER status.

Although exercise training is known to improve body composition, the molecular biomarkers and mechanisms related to these changes have not been fully elucidated. PURPOSE: The purpose of this study was to examine the associations between change in plasma proteins and change in body composition traits in response to endurance training. METHODS: Measurements were taken before and after 20 weeks of standardized, endurance training in Black and White adults of the HERITAGE Family Study (n = 652). Over 5,000 plasma proteins were measured using an aptamer-affinity based platform (SomaScan). Underwater weighing, CT scans, and anthropometric measurements were used to derive the 11 body composition traits included in this study: BMI, body surface area, fat mass, fat free mass , %fat, waist circumference, waist-to-hip ratio (WHR), body weight, and abdominal visceral, subcutaneous, and total fat. Linear mixed models were used to test the association between change in plasma proteins and change in each body composition trait adjusted for age, sex, race, baseline BMI, and baseline trait value with family membership as a random variable. Significance was set to FDR < 0.05. RESULTS: On average, subjects were 35% Black, 56% female, 35 years old, and overweight at baseline (mean BMI 26.4 (SD 5.3) kg/m2), with %fat of 27.5 (10.4). All 11 traits significantly improved in response to training. Significant associations between changes in proteins and body composition were found for all traits except WHR, with 57 unique proteins identified. Leptin was the top association (range: 0.023 < FDR p-value<4.2x10-12) for all 9 body composition traits it associated with (Table 1). CONCLUSIONS: Although dozens of proteins were associated with changes in body composition traits, 6 proteins were associated with ≥8 traits. Globally, these proteins are involved in pathways such as adipogenesis, energy balance, and cell growth, which may potentially influence body composition and fat distribution traits.

No abstract is provided for this article.

No abstract is provided for this article.