Showing papers by "Claude Bouchard published in 1997"

Physical Activity, Fitness, and Health

Abstract: Physical Activity, Fitness, and Health: Consensus Statement Claude Bouchard;Roy Shephard;Peter Brubaker; Medicine & Science in Sports & Exercise

Handbook of obesity

Abstract: History definitions and prevalence: historical framework for the development of ideas about obesity definitions and proposed current classification of obesity evaluation of total and regional body composition time trends in the worldwide prevalence of obesity prevalence of obesity in children obesity in the elderly. Etiology: the genetics of human obesity animal models of obesity molecular genetics of obesity diet composition and the control of food intake in humans experimental studies on the control of food intake behaviourial neuroscience of obesity. Pathophysiology: etiology of the metabolic syndrome clinical manifestations of the metabolic syndrome the effects of obesity on the cardiovascular system obesity and lipoprotein metabolism obesity and blood pressure regulation obesity and diabetes. Evaluation, prevention, and treatment: prevention of obesity classification and evaluation of the overweight patient behaviourial approaches to the treatment of obesity dietary treatment of obesity exercise as a treatment for obesity treatment of overweighed NIDDM patients. (Part contents).

Acute and chronic effects of exercise on leptin levels in humans

Abstract: Perusse, Louis, Gregory Collier, Jacques Gagnon, Arthur S. Leon, D. C. Rao, James S. Skinner, Jack H. Wilmore, Andre Nadeau, Paul Z. Zimmet, and Claude Bouchard. Acute and chronic effects of exerci...

Genetics of fitness and physical performance

Abstract: "Genetics of Fitness and Physical Performance" is the first comprehensive reference on the role of the genes in influencing individual variation in fitness and performance. This essential compendium reviews the past 25 years of accumulated evidence on the genetic basis of health- and performance-related fitness phenotypes. Focusing on the interests of sport scientists, the authors provide insight into the significance of this research on nearly every aspect of the study of human physical activity. The book presents the biological basis of heredity and explains the concepts and methods of genetic epidemiology and molecular biology that are necessary to understand this specialized field. With the rapid advances in molecular biology and the paradigms of human genetics, exercise scientists face a dynamic and vibrant new field. This book offers readers new opportunities to better understand atherosclerosis, noninsulin dependent diabetes, obesity, and hypertension by searching for single gene effects and identifying susceptibility genes.The authors review the evidence on the role of the genes for human traits as it pertains to the exercise science field. And they explore the scientific, practical, and ethical issues that confront exercise scientists as progress is made in this field."Genetics of Fitness and Physical Performance" is vital reading for scholars in the field of exercise and sport science to understand how recent discoveries in genetics might shape their future research.

Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q.

Abstract: Chromosomal synteny between the mouse model and humans was used to map a gene for the complex trait of obesity. Analysis of NZB/BINJ x SM/J intercross mice located a quantitative trait locus (QTL) for obesity on distal mouse chromosome 2, in a region syntenic with a large region of human chromosome 20, showing linkage to percent body fat (likelihood of the odds [LOD] score 3.6) and fat mass (LOD score 4.3). The QTL was confirmed in a congenic mouse strain. To test whether the QTL contributes to human obesity, we studied linkage between markers located within a 52-cM region extending from 20p12 to 20q13.3 and measures of obesity in 650 French Canadian subjects from 152 pedigrees participating in the Quebec Family Study. Sib-pair analysis based on a maximum of 258 sib pairs revealed suggestive linkages between the percentage of body fat (P < 0.004), body mass index (P < 0.008), and fasting insulin (P < 0.0005) and a locus extending approximately from ADA (the adenosine deaminase gene) to MC3R (the melanocortin 3 receptor gene). These data provide evidence that a locus on human chromosome 20q contributes to body fat and insulin in a human population, and demonstrate the utility of using interspecies syntenic relationships to find relevant disease loci in humans.

Linkage Between Markers in the Vicinity of the Uncoupling Protein 2 Gene and Resting Metabolic Rate in Humans

Abstract: The recent cloning of a gene that codes for a novel uncoupling protein, UCP2, which is expressed in a wide range of adult human tissues, has raised the possibility that it may be involved in regulation of energy balance. To explore this concept we have investigated potential linkage relationships between three microsatellite markers which encompass the UCP2 gene location on 11q13 with resting metabolic rate (RMR), body mass index, percentage body fat (%FAT) and fat mass (FM) in 640 individuals from 155 pedigrees from the Quebec Family Study. Using a linkage analysis strategy based on sibling, avuncular, grandparental and cousin pairs, strong evidence of linkage was found between the marker D11S911 (P = 0.000002) and RMR, with more moderate evidence for D11S916 (P = 0.006) and D11S1321 (P = 0.02). Suggestive evidence of linkage was also observed between D11S1321 and %FAT (P = 0.04) and FM (P = 0.02). It is concluded that the three markers encompassing the UCP2 locus and spanning a 5 cM region on 11q13 are linked to resting energy expenditure in adult humans. The evidence is strong enough to warrant a search for DNA sequence variation in the gene itself.

Abdominal Visceral Fat is Associated with a BclI Restriction Fragment Length Polymorphism at the Glucocorticoid Receptor Gene Locus

Abstract: Several investigations have suggested that body fat distribution is influenced by nonpathologic variations in the responsiveness to cortisol. Genetic variations in the glucocorticoid receptor (GRL) could therefore potentially have an impact on the level of abdominal fat. A restriction fragment length polymorphism (RFLP) has previously been detected with the BclI restriction enzyme in the GRL gene identifying two alleles with fragment lengths of 4.5 and 2.3 kb. This study investigates whether abdominal fat areas measured by computerized tomography (CT) are associated with this polymorphism in 152 middle-aged men and women. The less frequent 4.5-kb allele was found to be associated with a higher abdominal visceral fat (AVF) area independently of total body fat mass (4.5/4.5 vs. 2.3/2.3 kb genotype; men: 190.7 +/- 30.1 vs. 150.7 +/- 33.3 cm2, p = 0.04; women: 132.7 +/- 37.3 vs. 101.3 +/- 34.5 cm2, p = 0.06). However, the association with AVF was seen only in subjects of the lower tertile of the percent body fat level. In these subjects, the polymorphism was found to account for 41% (p = 0.003) and 35% (p = 0.007), in men and women, respectively, of the total variance in AVF area. The consistent association between the GRL polymorphism detected with BclI and AVF area suggests that this gene or a locus in linkage disequilibrium with the BclI restriction site may contribute to the accumulation of AVF.

Genetic Influences on the Response of Body Fat and Fat Distribution to Positive and Negative Energy Balances in Human Identical Twins

Abstract: This article summarizes a series of intervention studies conducted with pairs of young adult male identical twins and designed to determine whether there is any evidence for genotype x overfeeding or genotype x negative energy balance interaction effects in the changes in body weight, body composition, fat distribution, computerized tomography-assessed abdominal visceral fat, resting metabolic rate and thermic response to a standardized meal of mixed composition brought about by chronic exposure to appropriate experimental treatments. These studies demonstrated that individual differences in response to chronic alterations in energy balance are common. The comparison of the heterogeneity in response between the pairs of twins in contrast to the variance within pairs revealed that members of the same twin pair are significantly more alike than individuals who are not genetically related by descent. The intrapair resemblance in response was particularly strong for the changes in body mass, body composition, subcutaneous fat distribution and abdominal visceral fat. In contrast, the results of two long-term intervention studies showed that variations in resting metabolic rate following exposure to chronic overfeeding or negative energy balance induced by exercise were accounted for primarily by the changes in body mass. Finally, the thermic response to food was not modified by any of the experimental treatments. On the basis of these observations, we conclude that there are individuals at risk of gaining weight and body fat or who are resistant to weight loss. These differences in susceptibility to chronic overfeeding or in sensitivity to negative energy balance seem to be largely explained by genetic factors whose exact nature remains to be determined.

Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Québec Family Study.

Abstract: The agouti yellow mouse shows adult onset of moderate obesity and diabetes. A depressed basal lipolytic rate in adipocytes or a decreased adrenergic tone arising from antagonizing α-melanocyte-stimulating hormone (MSH) activation of melanocortin receptors (MCR) could be at the origin of the obesity phenotype. MCR 4 and 5 (MC4R, MC5R) genes were studied in the Quebec Family Study. Sequence variations were detected by Southern blot probing of restricted genomic DNA, and mRNA tissue expression was detected by RT-PCR. Subjects with a wide range of weight were used for single-point sib-pair linkage studies (maximum of 289 sibships from 124 nuclear families). Analysis of variance across genotypes in unrelated males (n = 143) and females (n = 156) was also undertaken. Body mass index (BMI), sum of six skinfolds (SF6), fat mass (FM), percent body fat (%FAT), respiratory quotient (RQ), resting metabolic rate (RMR), fasting glucose and insulin, and glucose and insulin area during an oral glucose tolerance test were analyzed. MC4R showed polymorphism with NcoI, and MC5R, with PstI and PvuII, with a heterozygosity of 0.38, 0.10, and 0.20, respectively. Linkages were observed between MC5R and BMI (p = 0.001), SF6 (p = 0.005), FM (p = 0.001), and RMR (p = 0.002), whereas associations were observed in females between MC5R and BMI (p = 0.003), and between MC4R and FM (p = 0.002) and %FAT (p = 0.004). After correction for multiple tests, these p values are lowered by one tenth. MC4R and MC5R mRNAs have been detected in brain, adipose tissue, and skeletal muscle. MC4R and MC5R exibit evidence of linkage or association with obesity phenotypes, but this evidence is strongest for MC5R.

Familial resemblance of plasma lipids, lipoproteins and postheparin lipoprotein and hepatic lipases in the HERITAGE Family Study.

Abstract: The familial aggregation of lipids and lipoproteins and plasma postheparin triglyceride lipases was investigated in 86 Caucasian families participating in the HERITAGE Family study, a study investigating the role of genetic factors in the adaptation to exercise training and its relationships with cardiovascular disease risk factors. Accordingly, sedentary subjects were recruited, tested for a battery of measurements, exercise trained for 20 weeks, and were re-measured. The present report includes plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides, and postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities measured in 437 sedentary individuals (171 parents and 266 adult offspring) before training. Significant familial resemblance was observed for all the age-adjusted phenotypes. The pattern of familial correlations reveals no spouse correlations but significant parent-offspring and sibling correlations for total cholesterol, HDL-cholesterol and LDL-cholesterol with heritability (h2) estimates of 62%, 83%, and 50%, respectively. For plasma triglyceride concentrations (h2 = 55%) and HL activity (h2 = 40%), significant spouse correlations were found in addition to parent-offspring and sibling correlations, suggesting that common familial environment in addition to genetic factors contribute to the familial resemblance. For plasma LPL activity, there was no spouse correlation, but sex differences were found in the familial correlations with higher heritabilities in female pairs (h2 = 76%) compared to male pairs (h2 = 30%) and opposite-sex pairs (h2 = 44%). These results confirm the findings of previous family studies showing that genetic factors are major determinants of the familial resemblance in plasma lipids and lipoproteins and suggest the presence of sex differences in the heritability of postheparin LPL activity.

Visceral fat in relation to health: is it a major culprit or simply an innocent bystander?

Abstract: The aim of this review is to look critically at the widely accepted notion that visceral fat accumulation is the main determinant of obesity related diseases. Most of the epidemiological evidence is based on anthropometric indicators of fatness and fat distribution and their implications for visceral fat accumulation may not be unequivocal. In most cross-sectional studies in which visceral fat is associated with the level of risk factors or presence of disease, no adjustment is made for potential confounders. There are potential confounders at different levels of the causal chains linking visceral fat to health. Firstly, there are aspects of body composition or fat depots associated with visceral fat accumulation such as total body fat or total subcutaneous fat. Total and subcutaneous fat are, by themselves, potentially strong determinants for metabolic disturbances and disease. Secondly, there are behavioural factors (for example smoking, alcohol consumption, physical activity, dietary habits) which have been found to be associated with both the amount of visceral fat and health outcomes. Thirdly, there are hormonal mechanisms (adrenal and gonadal steroids as well as growth hormone) which may affect both the accumulation of visceral fat as well as the development of diseases. Finally, even if associations between visceral fat and risk factors or presence of diseases would be firmly established, the causality of the observed associations may not always be easy to interpret. Prospective studies are needed with appropriate control of potential confounding variables. It is concluded that, based on the current evidence, it is difficult to quantify the independent contribution of visceral fat to the development of a variety of chronic diseases.

Plasma leptin concentrations: gender differences and associations with metabolic risk factors for cardiovascular disease

Abstract: The cloning of the obese gene and the characterization of its protein product, leptin, has permitted the study of a new hormone potentially involved in the regulation of adipose tissue mass. The present study examined the gender differences in fasting plasma leptin concentration and its relationship to body fatness, adipose tissue distribution and the metabolic profile in samples of 91 men (mean age ± SD: 37.3 ± 4.8 years) and 48 women (38.5 ± 6.8 years). Plasma leptin concentrations were strongly associated with body fat mass measured by underwater weighing [men: r = 0.80, p < 0.0001; women: r = 0.85, p < 0.0001]. In both genders, plasma leptin levels were also strongly correlated with waist girth as well as cross-sectional areas of abdominal subcutaneous and visceral adipose tissue measured by computed tomography. Women had, on average, plasma leptin concentrations that were three times higher than men. Furthermore, this gender difference remained significant when comparing men and women matched for similar levels of body fat mass. The associations between plasma leptin and lipoprotein concentrations were dependent of adiposity. In both men and women, elevated fasting plasma leptin levels were associated with higher plasma insulin concentrations, but only in women was the association maintained after correction for fat mass. Thus, results of the present study show that women have higher plasma leptin levels compared to men, independent of the concomitant variation in total body fat mass. Furthermore, our results also suggest that, in women, the association between plasma leptin and insulin concentrations is independent of adiposity, a finding which provides further support to the observation that adipose tissue leptin secretion may be upregulated by insulin. [Diabetologia (1997) 40: 1178–1184]

Familial resemblance for abdominal visceral fat: the HERITAGE family study

Abstract: OBJECTIVES: Abdominal visceral fat (AVF) is considered a risk factor for diabetes, atherogenic lipid profiles and hypertension. However, little is known about the genetic contribution to AVF as compared to total body fat. DESIGN: AVF was assessed by computerized tomography, and total body fat (fat mass) was assessed by underwater weighing in 86 families participating in the Heritage Family Study. All family members were sedentary at baseline examination. The familial factors underlying the variability in age-adjusted AVF, age-fat mass-adjusted AVF and age-adjusted fat mass, were assessed using a familial correlation model. RESULTS: The maximal heritability (including genetic and familial environmental effects) for AVF was comparable before (47%) and after (48%) adjusting for fat mass, and was 55% for fat mass itself in these sedentary families. Spouse correlations were significant for fat mass and for AVF prior to, but not after, adjustment for fat mass. CONCLUSIONS: These results confirm the only previous study which investigated the familial aggregation of AVF (both in pattern and magnitude), suggesting that the factors underlying AVF in these sedentary families may be similar to those in the population at large. Although both genetic and familial environmental factors probably influence each of fat mass and AVF, there appears to be a predominantly genetic etiology for the visceral component which is independent of total body fat. These findings imply that some individuals are more at risk than others because of an inherited tendency to store abdominal fat viscerally rather than subcutaneously.

Obesity in adulthood--the importance of childhood and parental obesity.

Abstract: Obesity is a common condition with delayed and usually late-onset consequences. Since the prevalence of obesity is high and still growing, it is important to understand who is at risk for becoming obese and for what reasons, so that preventive measures can be implemented. This is particularly important in the light of the dramatic increase in the prevalence of excess body mass in relation to height in children and adolescents during the past 30 years.1 Unfortunately, it is still not possible to determine which children will be obese as adults, which will be affected by the conditions commonly associated with . . .

Muscle-specific creatine kinase gene polymorphism and VO2max in the HERITAGE Family Study.

Abstract: This study examined the association between a DNA polymorphism in the muscle-specific creatine kinase (CKMM) gene and VO2max in the sedentary state, as well as its response (deltaVO2max) to a standardized 20-wk endurance training program. The subjects were 160 biologically unrelated Caucasian parents (80 women, 80 men) and 80 biologically unrelated adult offspring of the HERITAGE Family Study. The CKMM polymorphism was detected by PCR and digestion with the NcoI restriction enzyme. VO2max was measured during maximal cycle ergometer tests. VO2max was 2119 +/- 45 mL x min(-1) (mean +/- SE) or 26 +/- 0.4 mL x kg(-1) x min(-1). Both sexes had a significant (P 0.05) between sexes. Age and sex adjusted VO2max was significantly (P = 0.007) associated with the CKMM genotype in the parents, whereas no association (P > 0.05) was observed in the offspring. DeltaVO2max values adjusted for age, sex, VO2max, and body mass were characterized by genotype differences in both parents (P = 0.0004) and offspring (P = 0.0025). A significantly (P < 0.05) lower deltaVO2max to endurance training was detected in both parents and offspring homozygotes for the rare allele. The genotype accounted for at least 9% of the variance in deltaVO2max. These results indicate that the NcoI polymorphism in the 3' untranslated region of the muscle-specific creatine kinase gene is associated with the deltaVO2max to endurance training.

Genetic determinants of regional fat distribution

Abstract: Upper body fat and abdominal visceral fat are two obesity-related phenotypes of interest because of their relationships with a variety of metabolic complications. The heritability of the amount of upper body fat or the level of upper body fat relative to lower body fat ranges from approximately 30-50% of the phenotype's age, sex and total body fat adjusted variance. On the other hand, familial studies of abdominal visceral fat reveal that the familial transmission reaches > 50% of the age, sex and total body fat adjusted variance. Complex segregation analysis undertaken with a panel of nuclear families indicates that major genes may account for a significant fraction of the variance in upper body fat and abdominal visceral fat. Two intervention studies conducted with pairs of male identical twins have shown that changes in upper body fat and visceral fat are more similar within pairs than between pairs, either in phenotype increments when challenged by chronic overfeeding, or in adipose tissue losses after exposure to long-term negative energy balance conditions. The evidence accumulated to date is sufficient to justify undertaking a search for the specific genes and molecular markers involved in the heterogeneity commonly observed in human fat topography.

Genetics of Human Obesity: Recent Results from Linkage Studies

Abstract: Excess body fat or body mass relative to height aggregates in families. It is commonly recognized that this familial aggregation of human obesity is accounted for in part by a significant genetic component. Thus the genetic heritability of the obesity phenotypes accounts for ∼25-40% of the age- and gender-adjusted phenotypic variances. There is also growing evidence that single-gene effects can be detected under appropriate conditions. The focus of research has now shifted to candidate genes and DNA markers of various obesity phenotypes. To date, linkage results have been published from the Pima Indian Study, the San Antonio Family Heart or Diabetes Studies, the Paris Cohort of Obese Siblings, the University of Pennsylvania Family Obesity Study and the Quebec Family Study. The only genomic scan (with ∼600 markers) reported to date is that from the Pima Indian sibling study. In that study, the strongest evidence for linkage with body fat was with markers on chromosome 11q, 6p and 3p. Evidence for linkage with markers on 7q was obtained in all family studies with the only apparent exception being the Pima Indians. Our own results from the Quebec Family Study suggest that there are linkages between body fat, as assessed from hydrodensitometry, and markers on 1p32-p22. Other linkages have been reported in the past but they are generally based on smaller sample size and weaker evidence.

Monitoring high-intensity endurance exercise with heart rate and thresholds.

Abstract: 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 VO 2max test on ergocycle and a 90-min high-intensity ergocycle 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, FeO 2 , and FeCO 2 were stable during the period from 20 to 80 min, VO 2 was constant from 30 to 80 min, while work output, pulmonary ventilation, blood lactate, and VCO 2 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 VO 2 at the ventilatory threshold seem to be more suitable markers for that purpose.

Suggestive linkages between markers on human 1p32-p22 and body fat and insulin levels in the Quebec Family Study.

Abstract: A single-gene rodent mutation (diabetes) and a quantitative trait locus (dietary obese 1) mapped to the mid portion of mouse chromosome 4 have been related to obesity and/or insulin levels. Synteny relationships place their putative human homologs on 1p31 and 1p35-p31, respectively. In 137 sibships of adult brothers and sisters from the Quebec Family Study, genetic linkages between seven microsatellite markers from 1p32-p22 and various obesity- and diabetes-related quantitative phenotypes were examined using single locus sibpair linkage analysis. Suggestive linkages were observed between markers D1S476 and body mass index (p = 0.05), fat mass (p = 0.02), the sum of six skinfolds (p = 0.02), the insulin area after an oral glucose tolerance test (p = 0.02), and between the neighboring marker D1S200 and body mass index (p = 0.03), and fat mass (p = 0.009). Suggestive linkages were also observed between the more telomeric markers D1S193 and body mass index (p = 0.03), and between the neighboring marker D1S197 and fasting insulin level (p = 0.05). No linkage was observed with the trunk to extremity skinfolds ratio. These linkages suggest that human homologs of the mouse diabetes or dietary obese 1 and/or other genes in this interval on chromosome 1 play a role in the regulation of body mass, body composition, and insulin levels, but not of subcutaneous fat distribution.

Reproducibility of anthropometric and body composition measurements: the HERITAGE Family Study

Abstract: OBJECTIVE: To determine the reproducibility of anthropometric and body composition measures using the HERITAGE Family Study protocol. DESIGN: Anthropometric and body composition measures were obtained on three separate days within a 3-wk period at each of the four HERITAGE Clinical Centers. SUBJECTS: Sixty men and women representative of the HERITAGE subject population, 15 from each of four Clinical Centers. MEASUREMENTS: Anthropometric measures included eight skinfolds, three girths and one length; and body composition measures included stature, mass, hydrostatic weight, residual volume, and body density, from which relative fat, fat mass and fat-free mass were estimated. RESULTS: Reproducibility as determined by technical error, coefficient of variation, and intraclass correlations was very high for the total sample. For example, intraclass correlations for the total sample generally ranged from 0.95–0.99 for the anthropometric measures, and from 0.97–1.00 for the body composition measures. The results across Clinical Centers were in close agreement with each other and with the pooled data. CONCLUSIONS: The reproducibility of anthropometric and body composition measures using the HERITAGE Family Study protocol is sufficiently high that it should be possible to detect small changes in any of these measures and to determine the genetic basis of these changes consequent to a 20 wk endurance training program.

Muscle-specific creatine kinase gene polymorphisms in elite endurance athletes and sedentary controls

Abstract: The purpose of this study was to investigate the association between elite endurance athlete (EEA) status and two restriction fragment length polymorphisms (RFLPs) at the muscle-specific creatine kinase (CKMM) gene locus. Genomic DNA was extracted from white blood cells or lymphoblastoid cel

The Human Obesity Gene Map: The 1996 Update

Abstract: An update of the human obesity gene map up to October 1996 is presented. Evidence from Mendelian disorders exhibiting obesity as a clinical feature, single-gene mutation rodent models, quantitative trait loci uncovered in crossbreeding experiments with mouse, rat, and pig models, association and case-control studies with candidate genes, and linkage studies with genes and other markers is reviewed. All chromosomal locations of the animal loci are converted into human genome locations based on syntenic relationships between the genomes. A complete listing of all these loci reveals that only 4 of the 24 human chromosomes are not yet represented, i.e., 9, 18, 21, and Y. Several chromosome arms are characterized by the presence of several putative loci. The following arms include at least three such loci: 1p, 1q, 3p, 4q, 6p, 7q, 8p, 8q, 11p, 11q, 15q, 20q, and Xq. Studies with negative association and linkage results are also reviewed.

Familial resemblance for body composition measures: the HERITAGE Family Study.

Abstract: A sex-specific familial correlation model was used to assess the heritable contributions to several measures of body composition in 86 sedentary white families participating in the HERITAGE Family Study. For this study, sedentary families were recruited, tested for a battery of measures, endurance exercise trained for 20 weeks, and remeasured. This sample is unique in that activity level was controlled for in these families at baseline measurement. In this report, three body composition variables measured at baseline were analyzed, two indexing adiposity (total subcutaneous fat based on eight skinfold measurements [SF8] and percent body fat measured by underwater weighing techniques [%BF]) and one assessing fat free mass ([FFM] derived from underwater weighing). The maximal heritabilities for SF8 (34%) and %BF (62%) were consistent with those reported in previous studies. There were no sex nor generation differences in the familial correlations, and the spouse correlation was significant, consistent with the hypothesis that the familial aggregation reflects genetic and familial environmental factors. However, the results for FFM were very different. The most parsimonious pattern of familial resemblance was consistent with mitochondrial inheritance (i.e., mother-offspring and sibling correlations were equal and were larger than those for spouse and father-offspring pairs). Under the mitochondrial hypothesis, 39% of the variance was accounted for by familial/genetic effects. However, under a nonmitochondrial hypothesis, which could not be ruled out, 65% of the FFM phenotypic variance was accounted for by familial/genetic factors. This high heritability level, as compared with results from previous studies, is consistent with the hypothesis that activity may constitute an important environmental determinant of FFM. These alternative hypotheses for FFM warrant further investigation using complex multilocus-multitrait segregation models, which allow for major genetic, polygenic, and environmental sources of variance, as well as interactions among them.

Glucose metabolism in identical twins discordant for obesity. The critical role of visceral fat.

Abstract: Obesity, especially intraabdominally deposited fatness, is associated with reduced insulin sensitivity. However, it is not well established whether this association is confounded by genetic factors. We studied 23 monozygous twin pairs (14 female, 9 male), 33-59 yr old, who had, on the average, 18 kg intrapair difference in body weight. A 75-g oral glucose tolerance test with glucose and insulin measurements at 30-min intervals was performed, and fat distribution was determined with magnetic resonance imaging. The pairs were divided into two groups by the gender-specific median of the abdominal visceral fat area (AVF) in the obese co-twins. In the high-AVF pairs, the mean area under curve (AUC) for glucose (mmol x min/L) was 758 vs. 968 (P = 0.001), AUC for insulin (mU x min/L) was 4320 vs. 8741 (P = 0.001), and insulin sensitivity index (mg x L x L/mmol x mU x min) was 71.5 vs. 45.9 (P < 0.001) in the lean and obese co-twins, respectively. In the low AVF pairs, the mean AUC for glucose was 669 vs. 706 (not significant), AUC for insulin was 3323 vs. 4241 (not significant), and the sensitivity index was 85.2 vs. 73.7 (P = 0.04) in the lean and obese co-twins, respectively. In subjects who are genetically identical but who are discordant for body mass, only those who differ most in visceral fat level are characterized by major alterations in insulin sensitivity and glucose tolerance.

Body composition by DEXA in older adults: accuracy and influence of scan mode.

Abstract: Dual energy x-ray absorptiometry (DEXA) measures bone mineral content (BMC), bone mineral density (BMD), fat-free mass (FFM), and provides estimates of percent body fat. Changes in scan mode geometry (pencil beam vs array) may impact these measures and body composition estimates using multi-compartment models. Forty-one adults, ages 59-79 yr, were scanned in each mode and also underwent hydrostatic weighing and measurement of total body water (tritiated water dilution). The effect of scan mode on measurement of DEXA BMC, BMD, FFM, and percent body fat (DEXA %Fat) was examined. The effect of scan mode on percentage body fat determined by a 4-compartment body composition model (4 Comp %Fat) and comparison of DEXA %Fat and 4 Comp %Fat were also examined. BMC and DEXA %Fat were greater (1.3% and 3.9%, respectively, P < 0.01), and BMD and FFM were lower (1.1% and 1.9%, respectively, P < 0.01) with the array scan mode. The 4 Comp %Fat was significantly greater (0.2%) when the array scan mode measurements of total body bone mineral were used; however, these differences were physiologically inconsequential. Comparison between DEXA %Fat and 4 Comp %Fat measures revealed a total error of +/-5.0% in the older adults examined. These results indicate significant scan mode differences in total body BMC, BMD, FFM, and DEXA %Fat measurements and demonstrate the importance of using a single DEXA scan mode for clinical investigation, particularly with longitudinal studies. For all investigations with DEXA, the scan mode should be reported. Furthermore, the error associated with using DEXA alone to estimate percent fat in an older population suggests that this technique is unacceptable in a research setting.

Genetics of human obesity: research directions.

Abstract: Rapid strides in understanding the physiology controlling energy or nutrient intake and energy expenditure have complemented the search for the genetic basis of obesity. Several single gene defects are known that produce obesity in animals. All of these have been cloned within the past 4 years, providing a rich new base for understanding obesity. Since obesity is likely to be "multifactorial," a number of laboratories have used the quantitative trait locus (QTL) technique of genome scanning to identify candidate genomic regions and, eventually, genes that may influence body weight and body fat. So far, 18 QTLs have been identified in association with crossbreeding strains of mice or rats with variable susceptibility to obesity. A number of mendelian disorders are known to exist in humans, but no specific genes have yet been identified for them. The potential for inserting new genetic material into mammals has produced numerous transgenic mice with increased or decreased quantities of body fat. These model...

Familial aggregation of obesity, candidate genes and quantitative trait loci.

Abstract: This brief review covers the findings reported in 1996 and in the first 2 months of 1997 on the genetic epidemiology and the molecular markers of human obesity. Although relatively little new evidence has been published on the heritability and other genetic epidemiology characteristics of obesity and fat topography, more has been reported on candidate genes, positional candidate genes and quantitative trait loci. Two recent genome-wide scans have revealed that several molecular markers on different chromosomes were linked to obesity-related phenotypes. Little support for a role for specific candidate genes can be found at this time. A large number of rodent quantitative trait loci have been uncovered so far but they have not yet been systematically tested in human populations.

Somatotype and cardiovascular risk factors in healthy adults.

Abstract: Relationships between cardiovascular risk factors and Heath-Carter anthropometric somatotype components were considered in 642 healthy adults free from overt disease: 68 males and 177 females, 30-39 years, and 233 males and 224 females, 40-49 years of age. Risk factors included systolic and diastolic blood pressures (SBP, DBP), fasting glycemia (GLYC), triglycerides (TG), plasma cholesterol (CHOL), the high density lipoprotein cholesterol fraction (HDL-C), and the HDL-C/CHOL ratio. Correlations between risk factors and each somatotype component were calculated after controlling for the effects of the other two somatotype components. Correlations were generally low and at best moderate, with significant correlations ranging from -0.23 to +0.23 in males and -0.20 to +0.30 in females. The relationships were stronger in the older group, 40-49 years, but the pattern of correlations was different in men and women. Endomorphy tended to be positively related to risk factors in older females, whereas ectomorphy tended to be negatively related to risk factors in older males. Comparison of somatotypes of individuals at the extremes of the distributions for each risk factor (upper and lower tertiles) were generally consistent with the direction of the correlations. For each cardiovascular risk, those with a poorer profile tended to be more endomorphic and mesomorphic and less ectomorphic than those with a better profile, who were more ectomorphic and less endomorphic and mesomorphic. The association was more apparent in males than in females and more so in those 40-49 years of age than in the younger age group. Although the correlations suggest that body type is weakly associated with common cardiovascular risk factors in healthy men and women, somatotype associations are more apparent at the extremes of the distributions of specific risk factors. Am. J. Hum. Biol. 9:11-19 © 1997 Wiley-Liss, Inc.

Segregation analysis of abdominal visceral fat: the HERITAGE Family Study.

Abstract: A major gene hypothesis for abdominal visceral fat (AVF) level, both before and after adjustment for total body fat mass, was investigated in 86 white families who participated in the HERITAGE Family Study. In this study, sedentary families were tested for a battery of measures (baseline), endurance exercise trained for 20 weeks, and then remeasured again. The baseline measures reported here are unique in that the variance due to a potentially important environmental factor (activity level) was limited. AVF area was assessed at L4 to L5 by the use of computerized tomography scan, and total body fat mass was assessed with underwater weighing. For fat mass, a putative locus accounted for 64% of the variance, but there was no evidence of a multifactorial component (i.e., no polygenic and/or common familial environmental effects). For AVF area, both a major gene effect accounting for 54% of the variance and a multifactorial component accounting for 17% of the variance were significant. However, after AVF area was adjusted for the effects of total level of body fat, the support for a major gene was reduced. In particular, there was a major effect for fat mass-adjusted AVF area, but it was not transmitted from parents to offspring (i.e., the three transmission probabilities were equal). The importance of this study is twofold. First, these results confirm a previous study that suggested that there is a putative major locus for AVF and for total body fat mass. Second, the findings from the HERITAGE Family Study suggest that the factors underlying AVF area in sedentary families may be similar to those in the population at large, which includes both sedentary and active families. Whether the gene(s) responsible for the high levels of AVF area is the same as that which influences total body fat content remains to be further investigated.