Publications

Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 Years after Bariatric Surgery

Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk, but whether these benefits persist over time is unknown.

TELEVISION VIEWING PHYSICAL ACTIVITY AND FITNESS IN YOUTH 239

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.

Abstract 21: Accounting For Smoking Behavior In Genome-wide Analysis Of Obesity Phenotypes: The Giant (genetic Investigation Of Anthropometric Traits) Consortium

Obesity, especially central obesity, and cigarette smoking (SMK) are both important risk factors for cardiovascular disease (CVD). Yet, smokers often exhibit lower body mass index (BMI) and higher waist circumference (WC) compared to non-smokers; also, smoking cessation leads to weight gain. Genome-wide association (GWA) studies have identified genetic loci that are associated with risk of overall and central obesity; yet little is known about whether and how SMK influences the genetic susceptibility to obesity. This study aims to discover genetic loci that are associated with obesity, measured as BMI and WC adjusted for BMI (WC a ), and where the effects are hidden by SMK. We used results from 42 studies including up to 126,767 subjects with GWA data available through the GIANT Consortium. Each study employed three association models while considering smoking status (current vs. not current smokers): 1) SNP effects adjusted for SMK (SNPadjSmk), 2) SNP by SMK interaction effects (SNPxSMK), and 3) joint effect of SNP and the SNP x SMK interaction effect (SNPxSMK J ). Study specific results were combined by inverse-variance weighted fixed-effects meta-analyses of the study specific results in men and women separately and then combined sexes. A total of 53 SNPs for WC a reached genome-wide significance (GWS) (p<1E-8) by adjusting for and allowing for interaction with SMK (SNPadjSMK and SNPxSMK J ), 27 of these loci are novel for WC a . Additionally, SNPadjSMK and SNPxSMK J models identified a total of 49 SNPs associated with BMI that reached GWS, including 15 novel loci. While no loci reached GWS for SNPxSMK on BMI, one novel SNPxSMK association with WC a near PRNP reached GWS in women. PRNP is highly expressed throughout the CNS and especially the hippocampus, as are many obesity-related genes. PRNP also plays a role in the body’s response to oxidative stress, making it a likely candidate gene for interaction with smoking as well. Of the GWS SNPs, 47 WC a and 41 BMI loci are nearby (<500 kb) previously established loci for traits of interest (e.g. SMK, obesity, CVD, VAT, lipids, T2D, T1D and other anthropometrics). We identify one locus with strong evidence of interaction with SMK on obesity, and notably, we find several new loci associated with obesity by accounting for the influence of SMK. Our results highlight the importance of appropriately modeling genetic associations by considering known biological relationships between phenotypes and the environment.

GENDER DIFFERENCES IN PRE- TO POST-TRAINING CHANGES IN VENTILATORY THRESHOLD: THE HERITAGE FAMILY STUDY

542 This study examined the gender differences in response of the ventilatory threshold to 20 weeks (3x/wk) of supervised cycle ergometry training in a biracial population of men (n=232) and women (n=208), ages 17-65 years. Participants in the HERIT AGE Family Study completed a heart rate-based training program progressing from a heart rate associated with 55% VO2max for 30 min to training at 75% VO2max for 50 min. Ventilatory threshold (VT) was estimated using V-Slope and ventilatory equivalents methods. Percent change for pre-post training values for selected variables are listed in the Table below.TableAn ANOVA between men and women across pre- post-training (Sex X Time) revealed no interaction for change in VO2max (ml·kg−1·min−1). However, there were highly significant Sex X Time interactions (p<0.0001) for improvements in VO2 at VT (VO2VT), increases in relative VT (RVT=VO2VT/VO2max * 100), increases in watts at VT (WVT), and increases in maximal watts (WMx) achieved during the post-training cycle egrometry test. These data show similar improvements in VO2max for men and woman, but strong gender differences in submaximal training-induced changes in VO2 and work at VT. This suggests that submaximal measurements of aerobic fitness reveal different aspects of improvements in fitness than the "gold standard" of VO2max. Sponsored by NHLBI HL47317 and NIH MO1-RR000400.

Familial Aggregation of Amount and Distribution of Subcutaneous Fat and Their Responses to Exercise Training in the HERITAGE Family Study

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.

[Genetics, dietary management and nutritional adaptations].

Genetics and Genomics of Obesity

It is commonly recognized that the prevalence of overweight and obesity is increasing around the world and that the obese are becoming more severely obese. Current estimates suggest that there are more than one billion adults who are overweight or obese worldwide. Recognizing the threat associated with excess weight, the World Health Organization has identified overweight as one of the main risk factors for the overall burden of disease in the world and one of the top five in developed nations. There are four major classes of factors contributing to the ongoing epidemic of obesity, which is ultimately the result of widespread energy imbalance favoring storage of the energy surplus not expended. These four broad classes of factors can be labeled as follows: built environment, social environment, behavior, and biology. The book Progress in Molecular Biology and Translational Science, Volume 94 reviews the latest evidence for the contribution of genetic factors to the risk of obesity. It explores genes and pathways potentially involved and the behavior that they influence and the role of genetic variation in white and brown adipose tissue biology, excess adipose tissue mass, syndromic and nonsyndromic obesity cases, lipodystrophies the current understanding of the genetic basis of eating disorders, eating behavior, and physical activity level.

UTILITY OF THE MINNESOTA EATING PATTERN ASSESSMENT TOOL IN TRACKING DIETARY LIPID INTAKE DURING EXERCISE TRAINING 1665

The Eating Pattern Assessment Tool (EPAT) is a short, self-administered questionnaire designed to give health care providers a simple method for assessing dietary lipids intake for counseling purposes. The validity and reliability of this tool were previously demonstrated in an upper midwestern clinical population. The EPAT was used in the HERITAGE Family Study to track the consistency of dietary intake of fat and cholesterol by participants throughout a 20-week exercise training period. Participants were 390 sedentary individuals from 70 Caucasian and African-American families, aged 16 to 66 yrs, from 4 regions of North America. At baseline, participants completed both sections of the EPAT (PRE), filled out the Willett semi-quantitative food frequency questionnaire (FFQ), and had blood taken for a pre-training lipid profile. Subjects repeat-ed the EPAT at week 10 (MID) and at week 20 (POST). Section I of the baseline EPAT showed reasonably good, highly significant correlations (r=0.40 to 0.55) with fat and cholesterol items from the FFQ(P<.0001). However, no such correlations were found for Section II. Both sections of the PRE, and fat and cholesterol related items from the FFQ, were poorly correlated with plasma total cholesterol and its lipoprotein fractions. Intraclass correlations coefficients for PRE, MID, and POST scores reached 0.78 for Section I and 0.65 for Section II, coefficients comparable to those previously reported from a less diverse population not participating in an exercise program. We conclude that our study participants were consistent through-out the exercise program in their dietary intake of fat and cholesterol. Our results also confirm the repeatability of the EPAT and the validity of Section I in tracking dietary lipid intake in a diverse population during an extended exercise training study.

Evidence of QTLs on chromosomes 13q and 14q for triglycerides before and after 20 weeks of exercise training: The HERITAGE Family Study

Fasting triglyceride (TG) levels in total plasma and in lipoprotein subfractions were assessed both at baseline and after a 20-week exercise training intervention in 99 White and 101 Black families. A genome-wide multipoint variance component linkage analysis was performed separately by race, using 509 markers. The strongest evidence of linkage was for the TG subfractions of low-density lipoprotein (LDL-TG) and high-density lipoprotein (HDL-TG) rather than for overall levels of TG. For baseline levels, the maximum LOD score was 3.8 on 13q12–q14 with HDL-TG in Whites. Additional linkage evidence was found on 14q31 (LOD=3.2) and 10p14 (LOD=2.9) for baseline LDL-TG in Whites. Suggestive linkage signal at baseline in Whites was detected for HDL-TG (LOD=2.6) on 12q24 and for LDL-TG on 19p13. For training response in Whites, suggestive signal (LOD=2.2) was observed on 13q12–q14 with LDL-TG and for HDL-TG on 10q23. For Blacks, weak signals (LODs<2.0) were found either for baseline and responses to training, perhaps due to small sample sizes that reduced the power of the linkage analysis. These results represent the first report of linkage for the lipoprotein subfractions and for the lipid and lipoprotein responses to exercise training. It is interesting that the strongest signals were found for the LDL-TG and HDL-TG subfractions, given their particular relationships with the atherogenic lipid profile including dense LDL and HDL particles.

CETP genotypes and HDL-cholesterol phenotypes in the HERITAGE Family Study

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.

Physical activity, lipid and lipoprotein metabolism, and lipid transport.

Effect of the amount of body fat on the age-associated increase in serum cholesterol

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.

Identification des besoins perçus des adolescents lorsqu'ils réintègrent leur milieu scolaire suite à une absence prolongée occasionnée par le traitement médical d'un cancer

No abstract is provided for this article.

Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE Family Study

It has been suggested that genetic variation in the angiotensin-converting enzyme ( ACE) gene is associated with physical performance. We studied the association between the ACE insertion (I)/deletion (D) polymorphism and several fitness phenotypes measured before and after 20 wk of a standardized endurance training program in sedentary Caucasian ( n = 476) and black ( n = 248) subjects. Phenotypes measured were oxygen uptake (V˙o 2 ), work rate, heart rate, minute ventilation, tidal volume, and blood lactate levels during maximal and submaximal [50 W and at 60 and 80% of maximalV˙o 2 (V˙o 2 max )] exercise and stroke volume and cardiac output during submaximal exercise (50 W and at 60%V˙o 2 max ). The ACE ID polymorphism was typed with the three-primer PCR method. Out of 216 association tests performed on 54 phenotypes in 4 groups of participants, only 11 showed significant ( P values from 0.042 to 0.0001) associations with the ACE ID polymorphism. In contrast to previous claims, in Caucasian offspring, the DD homozygotes showed a 14–38% greater increase with training in V˙o 2 max ,V˙o 2 at 80% ofV˙o 2 max , and all work rate phenotypes and a 36% greater decrease in heart rate at 50 W than did the II homozygotes. No associations were evident in Caucasian parents or black parents or offspring. Thus these data do not support the hypothesis that the ACE ID polymorphism plays a major role in cardiorespiratory endurance.

Evidence for the existence of small eaters and large eaters of similar fat-free mass and activity level.

No abstract is provided for this article.

Effect of repeated electroconvulsive shocks on serotonergic neurons

The hypothermia induced by the serotonin (5-HT)1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was attenuated in rats that had received a cource of six electroconvulsive shocks (ECS) over a two-week period. The firing activity of dorsal raphe 5-HT neurons, as well as their responsiveness to microintophoretic applications of 5-HT and 8-OH-DPAT, was unaltered in ECS-treated rats. The electrically evoked overflow of [3H]5-HT from preloaded slices of guinea pig hypothalamus was unchanged after the same ECS treatment. The concentration-effect curves of the 5-HT autoreceptor agonist 5-carboxyamindotryptamine (0.1–100 nM) were similar in slices prepared from control and ECS-treated guinea pigs. In addition, the reduction in the evoked [3H]5-HT overflow obtained by increasing the stimulation frequency from 1 to 5 Hz, which is due to a greater activation of terminal 5-HT autoreceptors at the higher frequency, was not altered by the ECS treatment. The enhancing effects of the 5-HT autoreceptor antagonist methiothepin (0.1–1 μM) and of the 5-HT3 (0.1–1 μM) on the evoked [3H]5-HT overflow were unaltered by the ECS treatment. These results thus indicate that repeated ECS attenuates the 8-OH-DPAT- induced hypothermia in rats, as previously reported, but does not affect the firing activity of 5-HT neurons and the sensitivity of their somatodendritic 5-HT1A autoreceptors in the dorsal raphe. The function of 5-HT terminals in the guinea pig hypothalamus was also unaffected by repeated ECS. In conclusion, repeated ECS does not affect the function of 5-HT neurons at the cell body and nerve terminal.

The human gene map for performance and health-related fitness phenotypes

The aim of this paper is to describe the first human gene map for physical performance and health-related fitness traits based on the papers published until the end of 2000. Studies of candidate genes using case-control and other designs are reviewed. Quantitative trait loci from the limited evidence reported to date in genomic scans are also incorporated. Performance and fitness phenotypes in the sedentary state as well as their changes during exercise, if applicable, or in response to exercise training are considered. Physical performance traits include cardiorespiratory endurance indicators and muscular strength or muscular performance variables. Health-related fitness phenotypes are grouped under the following categories: hemodynamic traits; anthropometry and body composition; insulin and glucose metabolism; and lipids, lipoproteins, and hemostatic factors. A yearly update of this human gene map will be published.

Morphologie et métabolisme du tissu adipeux humain: Relations avec le sexe, la graisse corporelle et le niveau d'entrainement

In order to study human fat cell morphology and metabolism in both sexes, with different levels of fatness and physical training, 53 subjects (14 women and 39 men), 25.9 ± 7.6 (mean ± SD) years of age, weighing 64.8 ± 10.8 kg and with 14.8 ± 4.7% body fat were submitted to a biopsy of subcutaneous adipose tissue in the supra-iliac region. Average fat cell diameter (ACD) was assessed measuring at least 500 cells per subject. Basal (BL), epinephrine sub-maximal (10−5 M) (ESML) and epinephrine maximal (10−4 M) (EML) stimulated lipolysis have been determined on collagenase isolated fat cells. Female subjects have larger ACD (83.4 ± 12.3 μm vs. 62.5 ± 1.9 μm) (P ≤ 0.001) and lower BL, ESML, and EML than men (P ≤ 0.05). After control over age and sex of subjects, there were significant and negative correlations between all fatness indicators (ACD, fat mass in kg, percent body fat, sum of 9 skinfolds) and BL, ESML and EML. A completely randomized factorial ANOVA design revealed a significant effect of fatness level on BL, ESML and EML, but a non-significant trend for the effect of physical training on the same variables. It is concluded that lipolytic activity is more related to body fatness than to the training status. However, training tends to accentuate lipolytic activity as shown values of BL, ESML and EML found in the lean highly trained subjects of the study.