Publications

In an attempt to better understand the genetic basis of the metabolic syndrome, we have undertaken a series of studies on the familial aggregation in the clustering of the coronary heart disease risk factors which characterize this syndrome. In the present study, the hypothesis of shared genetic (pleiotropy) and/or environmental factors between body fat and blood lipids is investigated by examining cross-trait (eg, father’s body fat with his son’s blood lipid) familial resemblance between 4 indicators of body fat (body mass index [BMI], sum of 6 skin folds [SF6]) and fat distribution (the ratio of the trunk to extremity skin folds adjusted [TER-sf] and unadjusted [TER] for SF6), and 5 blood lipid variables (total cholesterol [CH], triglycerides [TG], cholesterol associated with high-density lipoproteins [HDL], the CH/HDL ratio and the difference between CH and HDL [CH-HDL]) measured in 1239 individuals from 309 families participating in the Quebec Family Study. A bivariate correlation model was used to obtain maximum likelihood estimates of cross-trait spouse, parent-offspring, and sibling correlations after adjustment of body fat and lipid data for the effects of age, separately in the four sex-by-generation groups. Likelihood ratio tests revealed the presence of significant ( P <.05) cross-trait resemblance between body fat (BMI and SF6) and all lipid traits except CH and also between fat distribution (TER and TER-sf) and CH/HDL and CH-HDL. Only sibling cross-trait correlations were significant for all body fat-lipid pairs of measures, with bivariate familiality estimates (ie, shared genetic and/or environmental factors) ranging from 8% to 40%. Although the hypothesis of genetic pleiotropy cannot be ruled out from the pattern of cross-trait correlations found in the present study, we conclude that environmental factors shared within sibships are probably more important than common genes in determining the covariation between body fat and blood lipids.

Ventilatory and lactate thresholds have been proposed as tools to establish the highest steady-state intensity sustainable during prolonged physical exercise. The purposes of this study were to clarify whether the intensity at the ventilatory threshold could be sustained during prolonged high-intensity exercise and if the corresponding work rate, pulmonary ventilation, and blood lactate concentration could also be maintained. Fifteen young and healthy male subjects were submitted to a ˙VO2max test on ergocycle and a 90-min high-intensity ergo-cycle endurance exercise test. During the 90-min exercise test, subjects were able to maintain an intensity corresponding to a heart rate 5 beats·min-1 lower than that predetermined from the ventilatory threshold. Heart rate, FeO2, and FeCO2 were stable during the period from 20 to 80 min. ˙VO2 was constant from 30 to 80 min, while work output, pulmonary ventilation, blood lactate, and˙VCO2 decreased significantly over the 90-min performance. These results show that physiological parameters near the ventilatory threshold are not interchangeable and that some cannot be used to monitor high-intensity long term exercise. Moreover, they clearly demonstrate that the blood lactate concentration fluctuates substantially during a 90-min endurance performance and cannot predict the highest work intensity that can be sustained during prolonged exercise without fatigue. However, heart rate and ˙VO2 at the ventilatory threshold seem to be more suitable markers for that purpose.

Objective: To investigate the association between the Trp64Arg polymorphism of the β3‐adrenergic receptor gene and changes in body composition in response to endurance training. Research Methods and Procedures: Adult sedentary white and black subjects participating in the HERITAGE Family Study were measured before and after 20 weeks on endurance training for the body mass index, fat mass, percentage of body fat, fat‐free mass, sum of eight skinfolds, and subcutaneous, visceral, and total abdominal fat areas. The association between the Trp64Arg polymorphism and the response phenotypes, computed as the difference between pre‐ and post‐training values, was tested by analysis of covariance separately in men and women. The gene by race interaction term was also tested. Results: No race differences were observed for allelic and genotype frequencies. Training resulted in significant reduction of body fat in both men and women. No association of the Trp64Arg polymorphism was observed with training‐induced changes for any of the body composition phenotypes in both men and women. Discussion: These results suggest that the Trp64Arg polymorphism of the β3‐adrenergic receptor gene is not related to changes in body composition in response to exercise training.

Associations between cholesteryl ester transfer protein (CETP) polymorphisms and high-density lipoprotein cholesterol (HDL-c) levels before and after 20 wk of endurance training were investigated in the HERITAGE Family Study. Plasma HDL-c, HDL(2)-c, HDL(3)-c, and apolipoprotein (apo)A1 levels were measured, and 13 CETP single nucleotide polymorphisms (SNPs) were genotyped in 265 blacks and 486 whites. Three haplotypes defined by SNPs at the -1337, -971, and -629 sites were strongly associated with baseline HDL-c levels in whites. Both C-1337T and C-629A were associated with baseline HDL-c (P < 0.001) and apoA1 (P < 0.01) when tested separately. However, only C-629A remained significant in a combined model. G-971A was not associated with HDL phenotypes, but showed significant interactions with C-629A (P = 0.002) on baseline traits. Genotype-by-sex interactions were observed at the -629 locus for HDL(3)-c (P = 0.004) and apoA1 (P = 0.02) training responses in whites. In women, the -629 A/A homozygotes showed greater increases in HDL(3)-c (P = 0.02) and apoA1 (P = 0.02) levels than the other genotypes. Finally, apolipoprotein E (APOE) genotype and the CETP C-629A locus contributed independently and in additive fashion to the HDL traits, explaining 6.0-8.8% of the variance. The CETP -1337T and -629A alleles are associated with higher baseline HDL-c and apoA1 levels. The beneficial effects of endurance training on plasma HDL(3)-c and apoA1 levels are evident in white women homozygous for the -629A allele. The CETP and APOE genotypes account for up to 9% of the variance in HDL-c phenotypes in the HERITAGE Family Study.

No abstract is provided for this article.

This study investigates the contribution of body fat stores on the age-associated increase in serum cholesterol and triglyceride levels. Percentage of body fat was measured by hydrostatic weighing, and serum cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were determined in a sample of 472 healthy men and women ages 18–50 years. In both sexes, body fat mass was significantly correlated with serum cholesterol (r = 0.21 in men and r = 0.24 in women, P < 0.01) and triglyceride (r = 0.33 in men and r = 0.24 in women, P < 0.01) levels. After adjustment for the association between age and serum cholesterol, no correlation was observed between body fat mass and serum cholesterol (r = 0.01 in men and r = 0.09 in women). After correction for age, serum triglyceride levels remained significantly correlated with body fat mass (r = 0.26 and r = 0.17 in men and women, respectively, P < 0.05). As body fat also increases with age, the possibility that a partial correlation coefficient procedure eliminated a portion of the age effect mediated by an age-related increase in fat, was addressed by performing further analyses. Within each sex subsample two sets of analyses were performed on (a) three groups of subjects individually paired for age but with different levels of body fat stores, and (b) three groups of subjects paired for the amount of body fat but differing in age. When subjects were paired for age, analysis of variance revealed a significant effect of increased body fat stores on serum triglyceride (P < 0.01 in men and P < 0.05 in women) but no effect on serum cholesterol and low-density lipoprotein cholesterol levels. However, when groups were paired for percentage body fat, a significant effect of age on serum cholesterol and low-density lipoprotein cholesterol was observed in men (P < 0.05 and P < 0.01) and in women (P < 0.01). These results suggest that factors other than the increase in adipose tissue stores are responsible for the increases in serum cholesterol and low-density lipoprotein cholesterol levels observed with age.

OBJECTIVE—To determine the effect of a 20-week endurance training program in healthy, previously sedentary participants on measures derived from an intravenous glucose tolerance test (IVGTT). RESEARCH DESIGN AND METHODS—An IVGTT was performed before and after a standardized training program in 316 women and 280 men (173 blacks and 423 whites). Participants exercised on cycle ergometers 3 days per week for 60 sessions. The exercise intensity was progressively increased from 55% Vo2max for 30 min per session to 75% Vo2max for 50 min per session. RESULTS—Mean insulin sensitivity increased by 10% (P &amp;lt; 0.001) following the intervention, but the variability in the changes was high. Men had larger improvements than women (P = 0.02). Improvements in fasting insulin were transitory, disappearing 72 h after the last bout of exercise. There were also significant mean increases in the glucose disappearance index (3%, P = 0.02) and in glucose effectiveness (11%, P &amp;lt; 0.001), measures of glucose tolerance and of the capacity of glucose to mediate its own disposal, respectively. The acute insulin response to glucose, a measure of insulin secretion, increased by 7% in the quartile with the lowest baseline glucose tolerance and decreased by 14% in the quartile with the highest baseline glucose tolerance (P &amp;lt; 0.001). The glucose area below fasting levels during the IVGTT was reduced by 7% (P = 0.02). CONCLUSIONS—Although the effects of structured regular exercise were highly variable, there were improvements in virtually all IVGTT-derived variables. In the absence of substantial weight loss, regular exercise is required for sustained improvements in glucose homeostasis.

Introduction: Regular exercise beneficially increases plasma HDL-C levels at the group level. However, variation in individual HDL-C responses to exercise highlight a need for predictive biomarkers of exercise response. Hypothesis: We hypothesized that baseline abundance of circulating proteins is predictive of HDL-C response to exercise and that identified proteins are part of a complex biological network of exercise response. Methods: We measured over 5,000 circulating proteins using an aptamer-affinity based platform (SomaScan) in 667 black and white adults from the HERITAGE Family Study. Fasting plasma HDL-C was measured at baseline and following 20 weeks of supervised endurance exercise training. To predict exercise induced changes in HDL-C using baseline abundance of circulating proteins, models were created using LASSO regression and a 70/30 training test data split with 10-fold cross validation. Biological pathways, networks, and functions involving proteins identified in predictive modeling were investigated by ingenuity pathway analysis (IPA) and integrated molecular pathway level analysis (IMPaLA). Results: Regular exercise significantly increased HDL-C in the sample by 1.5 ± 4.6 mg/dL (p&lt;0.0001), however marked inter-individual differences in response were present (range: -19.5 to +17.4 mg/dL). LASSO regression of circulating proteins only yielded a model of 120 proteins with similar but stronger predictive power to a model of 19 clinical traits (root mean square error = 4.52 and 5.3 mg/dL respectively). LASSO regression of both clinical and proteomic predictors resulted in a final model of baseline HDL-C and 116 circulating proteins, with an improved root mean square error of 4.11 mg/dL. Furthermore, this panel of 116 proteins was able to explain 40.0% of the variance in exercise induced changes in plasma HDL-C, while clinical predictors alone (including baseline HDL-C) explained only 3.9%. Pathway analysis of these 116 proteins identified several biological processes including pathways involved in the progression towards atherosclerosis, angiogenesis, mTOR signaling, and mitochondrial fatty acid synthesis. Conclusions: Circulating proteins may allow for prediction of exercise induced changes in HDL-C. Additionally, proteins predictive of HDL-C response to exercise are associated with important biological pathways and may provide insights into the molecular mechanisms of the benefits of regular exercise.

The relationship between time spent viewing television and physical activity and health-related fitness was evaluated in youth 9-18 years of age from the Quebec Family Study. The sample was divided into three age groups by gender: 9-12 (131 M, 95 F), 13-15 (124 M, 102 F), and 16+ (101 M, 87 F) years. Television viewing (TV time, min/day) was estimated over a typical week. Physical activity was quantified as estimated daily energy expenditure (EE) and energy expenditure in moderate-to-vigorous physical activity (MVPA) derived from the protocol of Bouchard et al. (Am J Clin Nutr 37: 461-467, 1983) for two week days and one weekend day. Fitness variables were PWC150(kpm/kg·min-1), knee extension strength (kg/kg), sit-ups(n/min), and sum of six skinfolds (mm). Correlations between TV time and EE and MVPA were low and not significant with no clear pattern by age group and gender (-0.03 to -0.15). Those between TV time and fitness were also low and generally not significant with no clear pattern by age and gender (PWC150,-0.29 to -0.05; sit-ups, -0.25 to +0.10; strength, -0.08 to +0.16; skinfolds,-.03 to +0.17). At the extremes, youth in the highest and lowest quartiles of TV time showed no consistent significant differences (ANCOVA, age as the covariate) in EE, MVPA and the four fitness items within each age group and gender. Similarly, youth in the highest and lowest quartiles of EE, MVPA and each fitness item did not consistently differ in TV time within each age group and gender. The results indicate that time watching television may have only a weak association with physical activity and fitness in youth.

Objective: Investigate the familial aggregation of amount and distribution of subcutaneous fat and their changes in response to endurance training. Research Methods and Procedures: A total of 483 sedentary subjects from 99 nuclear families were recruited, trained for 20 weeks of exercising on cycle ergometers, and measured before and after training for the following indicators of subcutaneous fat and fat distribution: trunk fat (TRUNK = sum of abdominal, subscapular, suprailiac, and midaxillary skinfolds), extremity fat (EXTREM = sum of biceps, triceps, thigh, and calf skinfolds), subcutaneous fat (SF8 = sum of the eight skinfolds), the trunk to extremity skinfolds ratio adjusted for SF8 (TER) and waist girth adjusted for body mass index (WAIST). The familial aggregation of the age‐ and sex‐adjusted baseline phenotypes and their responses to training (Δ) after adjustment for the baseline values was investigated using a familial correlation model. Results: Significant familial aggregation was observed for all the phenotypes measured at baseline and for ΔTRUNK and ΔWAIST. Transmissibility estimates reached about 30% to 35% for TRUNK, EXTREM, and SF8 and 50% for TER and WAIST. The transmissibilities of the response phenotypes were lower, ranging from 0% for ΔWAIST to 21% for ΔTRUNK and the pattern of familial correlations suggested a greater within‐ than between‐generation resemblance in the response. Discussion: This study suggests that the amount and distribution of subcutaneous fat strongly aggregates in families, whereas the response to exercise training is characterized by a moderate and more complex pattern of familial resemblance. We conclude that familial/genetic factors are more important in determining the amount and distribution of subcutaneous fat than their responses to exercise training.

No abstract is provided for this article.