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Showing papers by "Claude Bouchard published in 2004"


Journal ArticleDOI
TL;DR: The use of BMI and waist circumference for the prediction of risk factor clustering among children and adolescents has significant clinical utility and race and gender differences in the optimal thresholds were minimal.
Abstract: Objective. To derive optimal body mass index (BMI) and waist circumference thresholds for children and adolescents, to predict risk factor clustering. Design. Cross-sectional receiver operating characteristic curve analysis. Setting. The Bogalusa Heart Study, a community-based study of cardiovascular disease risk factors in early life. Participants. A total of 2597 black and white children and adolescents, 5 to 18 years of age, who were examined between 1992 and 1994. Main Outcome Measures. The presence or absence of ≥3 age-adjusted risk factors (low high-density lipoprotein cholesterol level, high low-density lipoprotein cholesterol level, high triglyceride level, high glucose level, high insulin level, and high blood pressure) was predicted from age-adjusted BMI and waist circumference values. Results. The areas under the receiver operating characteristic curves were significantly different from 0.5 for both BMI and waist circumference for all gender/race groups, ranging from 0.73 to 0.82. The optimal BMI thresholds were at the 53rd and 50th percentiles for white and black male subjects, respectively, and at the 57th and 51st percentiles for white and black female subjects, respectively. Similarly, the optimal waist circumference thresholds were at the 56th and 50th percentiles for white and black male subjects, respectively, and at the 57th and 52nd percentiles for white and black female subjects, respectively. The sensitivity and specificity at the thresholds were similar for all gender/race groups, ranging from 67% to 75%. Conclusions. The use of BMI and waist circumference for the prediction of risk factor clustering among children and adolescents has significant clinical utility. In this sample, race and gender differences in the optimal thresholds were minimal.

471 citations


Journal ArticleDOI
TL;DR: This is the tenth update of the human obesity gene map, incorporating published results up to the end of October 2003 and continuing the previous format.
Abstract: This is the tenth update of the human obesity gene map, incorporating published results up to the end of October 2003 and continuing the previous format. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTLs) from human genome-wide scans and animal crossbreeding experiments, and association and linkage studies with candidate genes and other markers is reviewed. Transgenic and knockout murine models relevant to obesity are also incorporated (N = 55). As of October 2003, 41 Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. QTLs reported from animal models currently number 183. There are 208 human QTLs for obesity phenotypes from genome-wide scans and candidate regions in targeted studies. A total of 35 genomic regions harbor QTLs replicated among two to five studies. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 272 studies reporting positive associations with 90 candidate genes. Fifteen such candidate genes are supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. Overall, more than 430 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. The electronic version of the map with links to useful sites can be found at http:obesitygene.pbrc.edu.

358 citations


Journal ArticleDOI
TL;DR: Results show that changes in the consumption of some specific food groups are associated with body-weight changes, which could help to improve obesity treatment and prevention.

166 citations


Journal ArticleDOI
TL;DR: In this paper, a 6-year randomized, controlled trial was conducted to determine whether progressive aerobic exercise compared with usual activity slowed progression of atherosclerosis in men in Eastern Finland.
Abstract: Background Although regular physical activity is recommended for prevention of cardiovascular diseases, no data are available on its antiatherosclerotic effects in the general population. Objective To determine whether progressive aerobic exercise compared with usual activity slows progression of atherosclerosis in men. Design A 6-year randomized, controlled trial. Setting Eastern Finland. Participants 140 middle-aged men randomly selected from the population registry. Intervention Low- to moderate-intensity aerobic exercise. Measurements Atherosclerosis was quantitated ultrasonographically as the mean intima-media thickness in the carotid artery at baseline and at years 2 through 6. Results On the basis of intention-to-treat analyses, a 19.5% net increase (P 0.2). The progression of intima-media thickness in the carotid artery did not differ between the study groups (P > 0.2). A subgroup analysis that excluded men taking statins showed that the 6-year progression of intima-media thickness, adjusted for smoking and annual measures of low-density lipoprotein cholesterol level, systolic blood pressure, and waist circumference, was 40% less in the exercise group (0.12 mm [95% CI, -0.010 to 0.26 mm]) than in the control group (0.20 mm [CI, 0.05 to 0.35 mm]). Limitations Only middle-aged white men were included. The intervention included mainly aerobic exercises. Conclusions Aerobic physical exercise did not attenuate progression of atherosclerosis, except in a subgroup of men not taking statins.

157 citations


Journal ArticleDOI
TL;DR: Findings suggest that a reduction in total adiposity and abdominal fat may be a means by which CRF attenuates the health risk attributable to obesity as determined by BMI and WC.
Abstract: Objective: We tested the following hypotheses in black and white men and women: 1) for a given BMI or waist circumference (WC), individuals with moderate cardiorespiratory fitness (CRF) have lower amounts of total fat mass and abdominal subcutaneous and visceral fat compared with individuals with low CRF; and 2) exercise training is associated with significant reductions in total adiposity and abdominal fat independent of changes in BMI or WC. Research Methods and Procedures: The sample included 366 sedentary male (111 blacks and 255 whites) and 462 sedentary female (203 blacks and 259 whites) participants in the HERITAGE Family Study. The relationships between BMI and WC with total fat mass (determined by underwater weighing) and abdominal subcutaneous and visceral fat (determined by computed tomography) were compared in subjects with low (lower 50%) and moderate (upper 50%) CRF. The effects of a 20-week aerobic exercise training program on changes in these adiposity variables were examined in 86% of the subjects. Results: Individuals with moderate CRF had lower levels of total fat mass and abdominal subcutaneous and visceral fat than individuals with low CRF for a given BMI or WC value. The 20-week aerobic exercise program was associated with significant reductions in total adiposity and abdominal fat, even after controlling for reductions in BMI and WC. With few exceptions, these observations were true for both men and women and blacks and whites. Discussion: These findings suggest that a reduction in total adiposity and abdominal fat may be a means by which CRF attenuates the health risk attributable to obesity as determined by BMI and WC.

132 citations


Journal ArticleDOI
TL;DR: The association between Ca(2+) intake, derived from the Willett FFQ, and overall and abdominal adiposity in Black and White men and women of the HERITAGE Family Study was examined and significant inverse associations appeared in Black men and White women.
Abstract: Calcium (Ca(2+)) intake may play a role in the regulation of body weight. Increased Ca(2+) intake has been associated with lower body weight, BMI, and adiposity measures in cross-sectional studies. We examined the association between Ca(2+) intake, derived from the Willett FFQ, and overall and abdominal adiposity in Black and White men and women of the HERITAGE Family Study. BMI, the percentage of body fat (%FAT), the sum of 8 skinfold thicknesses, computerized tomography total abdominal fat (TAF), abdominal visceral (AVF) and abdominal subcutaneous (ASF) fat, and waist circumference were measured in 362 men (109 Blacks, 253 Whites) and 462 women (201 Blacks, 261 Whites). Subjects were divided into tertiles of energy-adjusted Ca(2+) intake. Adiposity measures across tertiles were compared by ANOVA and also regressed against the energy-adjusted Ca(2+) intake to test for a linear trend. The strongest inverse associations appeared in Black men and White women. Black men in the high Ca(2+) intake group were leaner than those in the low Ca(2+) intake group: BMI 23.4 +/- 0.9 vs. 26.7 +/- 1.1 kg/m(2) (P = 0.01); for all other adiposity measures, P < 0.05. In White women, regression analyses showed significant inverse associations between Ca(2+) intake and BMI (P = 0.02), %FAT (P = 0.001), TAF (P = 0.006), AVF (P = 0.03), and ASF (P = 0.01). The percentage of fat of White men in the highest Ca(2+) intake group was significantly lower than in the lowest Ca(2+) group (P = 0.04). No significant associations were found in Black women. Low Ca(2+) intake may be associated with higher adiposity, particularly in men and White women.

132 citations


Journal ArticleDOI
TL;DR: It is indicated that a significant source of anxiety feelings involves inherited and acquired parameters of acetylcholine regulation that can be readily quantified, which can help explaining part of the human variance for state and trait anxiety.
Abstract: Anxiety involves complex, incompletely understood interactions of genomic, environmental, and experience-derived factors, and is currently being measured by psychological criteria. Here, we report previously nonperceived interrelationships between expression variations and nucleotide polymorphisms of the chromosome 7q21–22 acetylcholinesterase-paraoxonase 1 (ACHE-PON1) locus with the trait- and state-anxiety measures of 461 healthy subjects from the Health, Risk Factors, Exercise Training, and Genetics Family Study. The AChE protein controls the termination of the stress-enhanced acetylcholine signaling, whereas the PON protein displays peroxidase-like activity, thus protecting blood proteins from oxidative stress damages. Serum AChE and PON enzyme activities were both found to be affected by demographic parameters, and showed inverse, reciprocal associations with anxiety measures. Moreover, the transient scores of state anxiety and the susceptibility score of trait anxiety both appeared to be linked to enzyme activities. This finding supported the notion of corresponding gene expression relationships. Parallel polymorphisms in the ACHE and PON1 genes displayed apparent associations with both trait- and state-anxiety scores. Our findings indicate that a significant source of anxiety feelings involves inherited and acquired parameters of acetylcholine regulation that can be readily quantified, which can help explaining part of the human variance for state and trait anxiety.

127 citations


Book
01 Jan 2004
TL;DR: History, Definitions, and Prevalence - Historical Framework for the Development of Ideas About Obesity George A. Bray, Evaluation of Total and Regional Adiposity, Steven B. Heymsfield, and Robert Ross, Ethnic and Geographic Influences on Body Composition.
Abstract: History, Definitions, and Prevalence - Historical Framework for the Development of Ideas About Obesity George A. Bray, Evaluation of Total and Regional Adiposity, Steven B. Heymsfield, Richard N. Baumgartner, David B. Allison, ZiMian Wang, and Robert Ross, Ethnic and Geographic Influences on Body Composition Paul Deurenberg and Mabel Deurenberg-Yap Prevalence of Obesity in Adults - The Global Epidemic, Jacob C. Seidell and Aila M. Rissanen The Fetal Origins of Obesity, David J. P. Barker Pediatric Obesity - An Overview, Bettylou Sherry and William H. Dietz Obesity in the Elderly - Prevalence, Consequences, and Treatment Robert S. Schwartz Economic Costs of Obesity Ian D. Caterson, Janet Franklin, and Graham A. Colditz Etiology Genetics of Human Obesity Claude Bouchard, Louis P russe, Treva Rice, and D. C. Rao Molecular Genetics of Rodent and Human Single Gene Mutations Affecting Body Composition Streamson C. Chua, Kathleen Graham and Rudolph L. Leibel Rodent Models of Obesity David A. York Primates in the Study of Aging-Associated Obesity Barbara C. Hansen Behavioral Neuroscience and Obesity Sarah F. Leibowitz and Bartley G. Hoebel Experimental Studies on the Control of Food Intake Henry S. Koopmans Diet Composition and the Control of Food Intake in Humans John E. Blundell and James Stubbs Central Integration of Peripheral Signals in the Regulation of Food Intake and Energy Balance: Role of Leptin and Insulin L. Arthur Campfield, Fran oise J. Smith, and Bernard Jeanrenaud Development of White Adipose Tissue G rard Ailhaud and Hans Hauner Lipolysis and Lipid Mobilization in Human Adipose Tissue, Dominique Langin and Max LaFontan Lipodystrophy and Lipoatrophy Steven R. Smith Uncoupling Proteins Daniel Ricquier and Leslie P. Kozak. (Part contents).

118 citations


Journal ArticleDOI
TL;DR: P73T) located within the NMB gene showed significant associations with eating behaviors and obesity phenotypes, and the results suggest that NMB is a very strong candidate gene ofeating behaviors and predisposition to obesity.

95 citations


Journal ArticleDOI
TL;DR: The hypothesis that an increased muscle fiber hypertrophic effect of strength training is present in D-allele carriers is not supported.
Abstract: This study explores the associations between polymorphisms in two candidate genes—myostatin gene (MSTN or GDF8) and angiotensin-converting enzyme (ACE) gene—with interindividual differences in human muscle mass and strength responses to strength training. The MSTN AluI A55T (exon 1), BanII K153R, TaqI E164 K and BstNI P198A (all in exon 2) markers and the ACE insertion (I)/deletion (D) polymorphism were typed in 57 males [22.4 (3.7) years] who participated in a 10-week, high-resistance training program for the elbow flexors. Maximal strength, and maximal isometric and concentric elbow flexor torques were measured at baseline and after training. Information on muscle cross-sectional area of the upper arm was obtained by computer tomography scans. Only one individual was heterozygous for the MSTN BanII K153R variant. No allelic variant was detected at the other MSTN sites in this population. For the ACE I/D polymorphism, no evidence was found for an association of the D or I allele with baseline strength, isometric and concentric torque or arm muscle cross-sectional area [analysis of covariance (ANCOVA) 0.25

80 citations


Journal ArticleDOI
TL;DR: It was concluded that postmenopausal women taking ERT tended to have lower values of AVF and other indicators of body composition, a more favorable lipid profile, and a slightly reduced risk of the MS when compared with women not taking supplemental hormones.
Abstract: The purpose of this research was to investigate the effects of apriori estrogen replacement therapy (ERT) and endurance exercise training in postmenopausal women on abdominal visceral fat (AFV) and other selected variables related to body composition and the metabolic syndrome (MS). Forty-eight healthy and previously sedentary postmenopausal women (mean age, 54.3 years) who were enrolled in the HERITAGE Family Study (HFS) served as subjects. Of these 48 women, 18 were currently taking ERT and the remaining 30 were taking no supplemental estrogen (NHRT). Computed tomography (CT) scans were used to assess 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 while body fat percentage (%FAT) and total fat mass (FATM) was assessed using underwater weighing. Blood assays for HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglycerides (TG) were conducted at a Centers for Disease Control (CDC) certified laboratory, while blood pressure measurements were assessed using an automated system. All measurements were obtained in duplicate before and after a regimen of endurance exercise training. Analysis of variance (ANOVA) showed AVF to be an average of 31.6 cm(2) less in the women receiving ERT, but lost statistical significance when AVF was adjusted for FATM. Mean values for TAF, ASF, and waist girth were also less in the women receiving ERT, but only waist girth achieved statistical significance. No differences were found in BMI or %FAT, but mean WHR was 5% smaller in the ERT group. Baseline values for HDL-C was higher and LDL-C lower in the ERT group. Prevalence of the MS tended to be greater in the NHRT group, but did not achieve statistical significance. There were no differences in training responses in any of the body composition variables between groups, however, in the ERT group LDL-C decreased with training while TG increased. It was concluded that postmenopausal women taking ERT tended to have lower values of AVF and other indicators of body composition, a more favorable lipid profile, and a slightly reduced risk of the MS when compared with women not taking supplemental hormones. Also exercise training did not improve the overall MS status of either group, as LDL-C status improved in the ERT group while TG decreased in the NHRT group.

Journal ArticleDOI
TL;DR: At the same age and level of adiposity, Black men andWomen have less AVF than White men and women, and the field regression equations can be generalized to the diverse group of adults studied, both in an untrained and trained state.
Abstract: OBJECTIVE: To determine if the relationship between abdominal visceral fat (AVF) and measures of adiposity are different between Black and White subjects and to develop valid field prediction models that accurately identify those individuals with AVF levels associated with high risk for chronic disease. DESIGN: Cross-sectional measurements obtained from 91 Black men, 137 Black women, 227 White men, and 237 White women subjects, ages 17–65 y, who were participants in the HERITAGE Family Study, both at baseline and following 20 weeks of endurance training. MEASURMENTS: AVF, abdominal subcutaneous fat (ASF), abdominal total fat (ATF), and sagittal diameter (SagD) were measured by computed tomography (CT). Body density was determined by hydrostatic weighing and was used to estimate relative body fat. Arm, waist (WC), and hip circumferences and skinfold thickness measures were taken, and BMI was calculated from weight (kg) and height (m2). Since CT abdominal fat variables were skewed, a natural log transformation (Ln) was used to produce a normal distribution. The General Linear Model (GLM) procedure was used to test the relationship between AVF and two different groups of variables—CT and anthropometric. RESULTS: The AVF of White men and women was significantly higher than that of Black men and women, independent of BMI, WHR, WC, and age, and was greater for men than for women. The CT model showed that the combination of SagD, Ln (ASF), age, and race accounted for 84 and 75% of the variance in AVF in men and women, respectively. The anthropometric model provided two valid generalized field AVF prediction equations. The Field-I equation, which included BMI, WHR, age and race, had an r2 of 0.78 and 0.73 for men and women, respectively. The Field-II equation, which included BMI (women only), WC, age, and race, had an r2 of 0.78 and 0.72 for men and women, respectively. The field model equations became less accurate as the estimated AVF increased. CONCLUSIONS: (1) At the same age and level of adiposity, Black men and women have less AVF than White men and women. These differences are greater in men than in women. (2) The field regression equations can be generalized to the diverse group of adults studied, both in an untrained and trained state. However, their accuracy decreases with increasing levels of AVF.

Journal ArticleDOI
TL;DR: These are the first reported human quantitative trait loci for dietary energy and macronutrient intakes and may refine to identify potential candidate genes for energy and specific macronUTrient intakes that would be amenable to more detailed molecular studies.

Journal ArticleDOI
01 Jun 2004-Diabetes
TL;DR: Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals.
Abstract: We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. Similar interaction was observed in blacks (P = 0.046). Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals.

Journal ArticleDOI
TL;DR: This genome scan provides evidence for several QTLs influencing lipid and lipoprotein levels, and promising candidate genes were located in the vicinity of the genomic regions showing evidence of linkage.

Journal ArticleDOI
TL;DR: The FAO/WHO/UNU (1985) procedures may overestimate daily energy needs, particularly in sedentary individuals, however, DRI (2002) are probably more adapted to estimate real dailyEnergy needs in seditary and active subjects in comparison to the FAO /WHO/ UNU ( 1985) procedures.
Abstract: Objective: To measure daily energy expenditure (DEE) with indirect calorimetric facilities in sedentary and active subjects. To estimate daily energy needs with the FAO/WHO/UNU (1985) procedures (EDEE) and estimated energy requirement (EER) with the dietary reference intakes 2002 (DRI) in healthy adults with sedentary or high-activity conditions. To compare estimated daily energy needs with their measured values. Design: Two groups of healthy subjects were tested under sedentary or high-activity conditions. In both groups, resting energy expenditure was measured after a 12-h overnight fast. DEE and basal metabolic rate (BMR) values were also measured with indirect calorimetry and compared to the relevant predicted values. Physical activity level and BMR were also estimated. Subjects: A total of 45 sedentary (26 men and 19 women) and 69 active subjects (43 men and 26 women) aged 18–30 and 30–60 y. Results: Measured daily energy expenditure (MDEE) was significantly lower than EDEE in sedentary men and women and in active men for the two age groups considered (P<0.05). EER was significantly lower than EDEE in both sedentary and active subjects of each subgroup (P<0.05). Conclusions: The FAO/WHO/UNU (1985) procedures may overestimate daily energy needs, particularly in sedentary individuals. However, DRI (2002) are probably more adapted to estimate real daily energy needs in sedentary and active subjects in comparison to the FAO/WHO/UNU (1985) procedures.

Journal ArticleDOI
TL;DR: The strongest evidence of linkage was found on chromosomal regions 11p15 and 10q23 for VO2 max and MPO in the sedentary state and on chromosomes 1p31 and 5q 23 for their responsiveness to training.
Abstract: The purpose of this study was to identify regions of the human genome linked to maximal oxygen uptake (Vo2 max) and maximal power output (MPO), and their response to a standardized 20-wk endurance...

Journal ArticleDOI
TL;DR: Current and past dieters had higher scores for cognitive dietary restraint and disinhibition compared with non-dieters, and interventions aimed at preventing an increase in disin inhibition may be promising for long-term weight maintenance.
Abstract: The purpose of the present cross-sectional study was to compare eating behaviours (cognitive dietary restraint, disinhibition and susceptibility to hunger), dietary profile and physiological variables according to the practice of dieting: current dieting; history of dieting in the 10-year period that preceded the study; no dieting during the same period. Dieting history, anthropometric markers of adiposity, RMR, dietary profile (3 d food record) and eating behaviours (three-factor eating questionnaire) were determined in a sample of 244 men and 352 women. A greater proportion of women (31.8 %) than men (16.8 %) reported that they had been on a diet over the past 10 years (P=0.0001). In both genders, current and past dieters had a higher BMI (P<0.05) than non-dieters and current dieters had lower reported energy intakes than past dieters and non-dieters (only in women) (P<0.05). Current and past dieters also had higher scores for all eating behaviours and their subscales (P<0.05; except for susceptibility to hunger in men) compared with non-dieters (adjusted for age, reported energy intake, percentage of dietary fat, BMI and RMR). Moreover, for each dieting-history category, women had significantly higher scores for cognitive dietary restraint than men (P<0.05). In conclusion, the present study showed that current and past dieters had higher scores for cognitive dietary restraint and disinhibition compared with non-dieters. As disinhibition has previously been associated with a greater risk of subsequent weight gain, interventions aimed at preventing an increase in disinhibition may be promising for long-term weight maintenance.

Journal ArticleDOI
TL;DR: The results suggest that in men, the human resistin gene is associated with reduced amount of visceral obesity and lower insulin secretory responses to a glucose load.
Abstract: Obesity and insulin resistance are common features of Type 2 Diabetes. A new protein called resistin has been shown to be secreted by adipocytes in mice and to influence insulin sensitivity. The goal of the present study was to investigate the associations between one polymorphism (g-420C>G) of the human resistin gene and phenotypes related to adiposity and glucose metabolism. We genotyped 725 (including 42 diabetics) adult subjects participating in the Quebec Family Study (QFS) by a minisequencing method. Forty-two were diabetic subjects. Phenotypes measured were: body mass index (BMI) and waist circumference (WC), % body fat (PFAT) and fat mass (FM) assessed by under water weighing, abdominal total, subcutaneous and visceral fat assessed by computed tomography and fasting plasma glucose, insulin and C-peptide and their responses to an oral glucose tolerance test (OGTT). Comparisons between genotypes were performed in non-diabetic men (no.=280) and women (no.=403) separately by analyses of covariance (ANCOVA). Among men, g-420 G homozygotes had less visceral fat (p<0.05), lower levels of acute insulin responses to an OGTT and lower levels of C-peptide in a fasting state and in responses to an OGTT than carriers of the C allele (p<0.01). These associations were independent of age and adiposity but were not observed in women. These results suggest that in men, the human resistin gene is associated with reduced amount of visceral obesity and lower insulin secretory responses to a glucose load.

Journal ArticleDOI
TL;DR: Racial and sex differences were noted in lipid responses to exercise training across genotypes with a significantly greater increase in HDL cholesterol observed only in white female carriers of apo E 2/3 and E3/3, as compared to apoE4/4.
Abstract: The relationship of apolipoprotein E (apo E) genotypes to plasma lipid and maximal oxygen uptake (Vo(2max)) was studied in the sedentary state and after a supervised exercise training program in black and white men and women. At baseline, the apo E 2/3 genotype was associated with the lowest, and apo E 3/4 and E4/4 with the highest low-density liporpotein (LDL) cholesterol and apo B levels in men and women of both races, while female (not male) carriers of apo E3 had higher high-density lipoprotein (HDL) cholesterol levels than carriers of other genotypes. Very-low-density lipoprotein (VLDL) cholesterol and triglyceride levels were significantly higher in carriers of both apo E2 and apo E4 in white men only. Racial and sex differences were noted in lipid responses to exercise training across genotypes with a significantly greater increase in HDL cholesterol observed only in white female carriers of apo E 2/3 and E3/3, as compared to apo E4/4. Apo E polymorphism was not found to be associated with Vo(2max) levels either in the sedentary state nor the Vo(2max) response to exercise training, contrary to previous reports.

Journal ArticleDOI
TL;DR: Studies of monozygotic twins in the context of overfeeding and energy deficit experiments have shown that gene–environment interactions affect energy balance, implying that some individuals are more susceptible to body-weight gain or loss than others because of genetic differences.
Abstract: Studies of monozygotic twins in the context of overfeeding and energy deficit experiments have shown that gene-environment interactions affect energy balance. From a clinical standpoint, this implies that some individuals are more susceptible to body-weight gain or loss than others because of genetic differences. This opens new perspectives in predictive medicine. In the future, health professionals should be able to count on early diagnosis of individuals at risk for developing long-term metabolic problems and obesity or for not responding adequately to clinical interventions. However, before predictive medicine is in a position to contribute significantly to prevention or treatment of patients, an enormous amount of work has to be done to identify all genetic and environmental factors of relevance, and their network of interactions.

Journal ArticleDOI
TL;DR: An overfeeding experiment conducted with 12 pairs of young male identical twins revealed that genetic factors were likely to play an important role in the response to caloric affluence, and an adipsin polymorphism was associated with increases in body weight, total fat mass and subcutaneous fat in response to overfeeding.
Abstract: Summary An overfeeding experiment conducted with 12 pairs of young male identical twins revealed that genetic factors were likely to play an important role in the response to caloric affluence. Significant intrapair resemblance was observed for the overfeeding-induced changes in body weight, fat mass, abdominal fat, fasting insulin, fasting cholesterol and triglycerides. In an attempt to define the molecular basis of these genotype–energy balance interaction effects, a panel of candidate genes has been investigated. Among the most significant findings, an adipsin polymorphism was associated with increases in body weight, total fat mass and subcutaneous fat in response to overfeeding. In addition, the beta2 adrenergic receptor gene Gln27Glu polymorphism showed a strong association with the gains in body weight and subcutaneous fat. Only a few markers were related to abdominal fat changes and, among them, the adipsin Hinc II polymorphism was associated with both computed tomography (CT)-measured abdominal visceral and total fat. The changes in insulin parameters brought about by long-term overfeeding were influenced most consistently by leptin receptor (LEPR) Gln223Arg and insulin-like growth factor-II Apa I polymorphisms. The LEPR Gln223Arg variant was also associated with the changes in plasma total triglycerides and high-density lipoprotein cholesterol concentrations. Further research with larger sample sizes should make it possible to identify the specific contributions of DNA sequence variations at multiple candidate gene loci in the complex response to chronic positive energy balance.

Journal ArticleDOI
TL;DR: It is concluded that when estimating the extent of inter-individual differences in training response, allowance must be made not only for the minor effects of recognized covariates, but also for the larger influence of test–retest measurement errors.
Abstract: Published reports have shown large apparent inter-individual differences of gains in maximal oxygen intake (VO2max) in response to a standard 20-week programme of aerobic conditioning that progressed to 75% of the individual’s initial VO2max. The observed gains of VO2max ranged from 0 to 1,000 ml min−1, with a coefficient of variation (CV) of 8.4%. The present analysis evaluates the potential contribution of test–retest errors to these apparent large inter-individual differences in training response. The 2-day test–retest CV for VO2max readings in 742 healthy adults was initially 5.0%, dropping to 4.1% after training. Published training responses were estimated from the mean of paired measurements obtained before and after training if readings agreed by 5%. Taking account of the relative proportions of single and paired observations, the weighted VO2max data for the entire sample had an effective 2-day CV of 4.3% before and 3.4% after training. Assumption 1: if the 20-week test–retest error remained similar to the 2-day figure, measurement error would contribute a CV of 5.5% to apparent training responses, or (for the stated initial mean VO2max of 2,409 ml min−1) an SD of 132 ml min−1. Assumption 2: if the 20-week CV was similar to that in other long-term studies (~5%), measurement error would contribute a CV of 6.1%, or a SD of 146 ml min−1. The published data show a total SD of 202 ml min−1 for apparent inter-individual differences in training response, with age, gender, race and baseline VO2max accounting for only 11% of this variance. After estimating the likely effect of test–retest measurement errors, the SD due to inter-individual differences would decrease to 138 ml minVO2max (assumption 1) or 123 ml min−1 (assumption 2). We conclude that when estimating the extent of inter-individual differences in training response, allowance must be made not only for the minor effects of recognized covariates (age, gender, race and initial fitness), but also for the larger influence of test-retest measurement errors. Nevertheless, substantial inter-individual differences persist after making such adjustments. The most likely explanation of these differences is a familial aggregation of training responses.

Journal ArticleDOI
TL;DR: In this paper, the relationship between abdominal fat and risk factors for cardiovascular disease (CVD) among normal-weight (NW) white subjects and to determine how these relationships differ by sex was investigated.
Abstract: The objectives of this study are to investigate the relationships between abdominal fat and risk factors for cardiovascular disease (CVD) among normal-weight (NW) white subjects and to determine how these relationships differ by sex. NW adults (177 males and 258 females) and overweight adults (133 males and 111 females) from the Quebec Family Study and the HERITAGE Family Study were retained for this study. Risk factors included systolic and diastolic blood pressures, low-density lipoprotein and high-density lipoprotein cholesterols, triglycerides, and fasting glucose. Only in NW female adults, abdominal visceral fat (AVF) area assessed by computed tomography was significantly correlated with all risk factors, except for fasting glucose, even after age, study cohort, and fat mass were taken into account. NW female subjects with at least one risk factor had a significantly higher AVF than those without risk factors, although the difference was small. Thus, only NW female adults with more AVF tended to have a more adverse CVD risk factor profile.


Journal ArticleDOI
TL;DR: A database containing the results from whole-genome scans of lipid-related phenotypes undertaken to date is created, and concerns arise when displaying all data on the same map, because a large portion of the genome is now covered with loci supported by at least suggestive evidence of linkage.

Journal ArticleDOI
TL;DR: The multivariate associations among fat loss and changes in blood lipids consequent to aerobic exercise training are similar in black and white men and women.
Abstract: PURPOSE This study explores sex and race differences in the association between changes in fat mass (FM), abdominal visceral fat (AVF), and abdominal subcutaneous fat (ASF) on blood lipid changes consequent to aerobic exercise training. METHODS The sample included 613 participants (428 white and 185 black, 46% men) from the HERITAGE Family Study. Total FM was determined by densitometry, whereas AVF and ASF cross-sectional areas were determined by computed tomography at the L4-L5 level. Blood lipid measurements included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and the TC/HDL-C ratio, which were obtained before and after 20 wk of supervised aerobic exercise. Canonical correlation was used to determine the multivariate associations between body fatness and blood lipids at baseline and the changes induced by exercise training. RESULTS Body fat accounted for 26-36% of the variance in baseline blood lipids, and changes in body fat accounted for 7-21% of the variance in changes in blood lipids with exercise training. The pattern of loadings indicated similar relationships between body fatness and blood lipids at baseline, and their respective changes with exercise training among the four sex-by-race groups. Greater fat loss, characterized by loss of FM, AVF, and ASF, was associated with a greater blood lipid response characterized by an increase in HDL-C and decreases in LDL-C, TG, TC, and TC/HDL-C. Although the pattern of loadings was similar in all groups, the strength of the association was stronger in blacks than in whites. CONCLUSION The multivariate associations among fat loss and changes in blood lipids consequent to aerobic exercise training are similar in black and white men and women.

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TL;DR: The findings suggest that favorable changes in the lipid profile can be obtained through chronic negative energy balance achieved by clamping daily energy intake and adding daily moderate intensity exercise even in persons with relatively normal lipid levels at baseline.

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TL;DR: A novel SNP, −3019G>A, is reported in the promoter of hAgRP, which is in complete linkage disequilibrium (LD) with the −38C>T SNP (linked alleles), potentially determining the net functional effect between these two SNPs.
Abstract: The agouti related protein (AgRP) exerts its anabolic effects on food intake by antagonising the alpha-melanocyte stimulating hormone (alpha-MSH) at its receptors, melanocortin receptors 3 and 4 (MC3R and MC4R). A single nucleotide polymorphism (SNP) in the promoter of the human AgRP (hAgRP), -38C>T, was associated with low body fatness. The -38T allele that was associated with low body fatness also resulted in lower promoter activity. Here we report a novel SNP, -3019G>A, again in the promoter of hAgRP, which is in complete linkage disequilibrium (LD) with the -38C>T SNP (linked alleles: -3019A/-38T and -3019G/-38C). Functional analyses in a human adrenal and two mouse hypothalamus cell lines showed that the -3019A allele had significantly higher promoter activity. Hence, the two linked alleles (-3019A and -38T) had opposite effects on promoter function and yet they were both associated with low body fatness. The region encompassing the -38C>T SNP had approximately 1000-fold higher activity than the region encompassing the -3019G>A SNP, potentially determining the net functional effect between these two SNPs.

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TL;DR: The results strongly suggest that the response of plasma lipoproteins to chronic energy surplus has a significant genetic component as does the detrimental effect of chronic caloric affluence on CHD risk.