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Biomedical subjects

C Bouchard

Publications and source records attributed to C Bouchard.

At least 397 records · Page 22Linked to original sources

DNA polymorphism in the uncoupling protein (UCP) gene and human body fat.

The objective of this study was to identify DNA sequence variation in the UCP gene and to investigate its relationship with some obesity phenotypes. Two studies were carried out: (1) association study in unrelated subjects, and (2) sib-pair linkage analysis study in brothers and sisters. The subjects were 261 individuals from the Québec Family Study (123 parents and 138 offsprings from 64 families). The following were measured: Body mass index, percent body fat (measured by hydrostatic weighing), and subcutaneous fat (estimated by the sum of 6 skinfolds) were measured in 1978-81 and again 12 years later. Resting metabolic rate (RMR) was measured only in 1989-93. Genetic analyses were performed using Southern blotting technique and a human UCP genomic probe. (1) A BcII restriction fragment length polymorphism was identified with two alleles of 8.3 and 4.5 kb in length, and respective frequencies of 0.28 and 0.72. (2) In unrelated adults from the parental generation, a cross-sectional analysis of the 1989-93 data showed no difference in body fat and RMR between the UCP genotypes. No significant difference for the absolute changes in body fat over the 12-year period among the UCP genotypes was observed. However, a higher frequency (P < 0.05) of the 8.3-kb allele was found in high gainers compared to low gainers (i.e., above and below the median value) for percent body fat over the 12-year period. (3) No evidence of linkage between any of the obesity phenotypes and the UCP BcII marker was found. For the first time, the presence of DNA polymorphism in the human UCP gene is reported. Although, no significant association and linkage were found between the UCP BcII gene marker and body fat in the cohort of the Quebec Family Study, a higher frequency of the 8.3-kb allele was found in individuals who gained more body fat over time.

Adipose Tissue↗

Cross-trait familial resemblance for body fat and blood pressure: familial correlations in the Québec Family Study.

Cross-trait resemblance between body fat and blood pressure (BP) was examined among families in the Québec Family Study by using a bivariate familial correlation model assessing both intraindividual (e.g., comparison of father's body fat with his own BP) and interindividual (e.g., comparison of father's body fat with son's BP) cross-trait correlations. Each of six body-fat measures-(i) percent body fat, (ii) body-mass index, (iii) the sum of six skinfolds, (iv) the ratio of the sum of six skinfolds to total fat mass, (v) the ratio of the trunk skinfold sum to the extremity skinfold sum, and (vi) the regression of the trunk-extremity skinfold ratio on the sum of six skinfolds--was analyzed separately with systolic BP and with diastolic BP. Results showed that (1) upper-body fat was the strongest interindividual correlate of BP (especially the correlation of trunk-extremity ratio with diastolic BP), suggesting shared pleiotropic genetic and/or common familial environmental effects; (2) summary body-fat measures either were inconsistent (in the case of both percent body fat and sum of six skinfolds) or gave no evidence of interindividual cross-trait resemblance with BP (in the case of body-mass index); and (3) intraindividual resemblance between the sum of six skinfolds and BP largely vanished once the skinfold sum was adjusted for fat mass, suggesting that the intraindividual association may be mediated largely by the absolute amount of subcutaneous fat rather than by the subcutaneous proportion. Finally, the magnitude of the spouse resemblance for the trunk-extremity ratio with diastolic BP suggests that a significant proportion of the resemblance may be due to environmental influences. In summary, our investigation confirms a heritable link between BP and truncal-abdominal fat as predicted by the metabolic-syndrome hypothesis. That this result is obtained in primarily normotensive, nonobese families, suggests the connection involves normal metabolic paths.

Adipose Tissue↗

Twin resemblance in somatotype and comparisons with other twin studies.

Twin resemblance in somatotype components was considered in 28 male and 34 female monozygotic (MZ) twin pairs and 19 male and 21 female dizygotic (DZ) twin pairs, 9.3-23.5 years of age. The Heath-Carter anthropometric somatotype method was used. Mean somatotypes of male twins and female twins did not differ, whereas male twins were significantly more mesomorphic than female twins. Twin resemblance was evaluated in two ways: first, treating each somatotype component independently of the other two (as in earlier twin studies), and, second, looking at resemblance in each somatotype component after statistically controlling for the other two components (thus treating the somatotype as a composite). Intraclass correlations were consistently higher in MZ than in DZ twins of both sexes, and within-pair variances were consistently lower in MZ than in DZ twins of both sexes. However, after controlling for the effects of the other two somatotype components, within-pair variances of male MZ and DZ twins for each somatotype component did not differ. In general, Heath-Carter anthropometric somatotype components show (1) significant resemblance in MZ and DZ twins within each sex, although the degree of resemblance is altered in male twins when a different analytic strategy is used, (2) no sex difference in degree of resemblance, and (3) greater resemblance within MZ twin pairs than within DZ twin pairs. These results are compatible with the presence of genetic variation affecting physique in adolescents and young adults.

Adolescent↗

The natural history of obesity in an obese population and associations with metabolic aberrations.

The natural history of obesity was examined in a nation-wide sample of 1,084 obese men and 1,367 obese women aged 37-59 years who were recruited into a registry of potential subjects for an intervention trial. The registry and intervention studies are jointly referred to as SOS ('Swedish Obese Subjects'). In the registry, the mean body mass index was 37.7 kg/m2 in men and 40.9 kg/m2 in women. Descriptive information on subjects' weight histories and the relative weights of their biological parents was collected by means of a self-administered questionnaire. At a physical examination shortly thereafter, weights, heights and selected cardiovascular risk factors were measured in the fasting state. Virtually all subjects reported weight loss attempts in the past, men and women reported having gained weight during adulthood at a considerably higher rate than that observed in population-based samples. Significant correlations were observed between relative weights of obese males and both of their biological parents, but not between obese women and either of their parents. Indices of medical risk were then examined in relation to individual weight histories. Familial predisposition did not relate to most aspects of current medical risk. However, later-onset obesity tended to be associated with greater cardiovascular risk, while prior weight loss was predictive of an improved risk factor profile. These latter associations were not dependent on a subject's current degree of obesity and were particularly consistent with respect to fasting insulin level.

Adult↗

Vulvar vestibulitis syndrome: an exploratory case-control study.

OBJECTIVE: To assess the prevalence of genital bacterial infection among women with vulvar vestibulitis syndrome and to evaluate the association of several potential risk factors with the occurrence of the syndrome. METHODS: Fifty-seven women referred for dyspareunia who satisfied Friedrich's criteria and had symptoms for at least 6 months were recruited as cases. Controls included 173 patients without dyspareunia seen at a private clinic. Cases and controls were aged 18-35 years and were not pregnant. RESULTS: Among cases, the prevalences were low for genital infection with gonorrhea (0%), Chlamydia (0%), Trichomonas (0%), Mycoplasma (0%), Gardnerella (14%), and Candida (8.8%). Ureaplasma was detected in the Bartholin glands of ten affected women (17.5%). Human papillomavirus DNA was detected in only three cases (5.3%) based on polymerase chain reaction assays on vestibular biopsies. The relative risk (RR) of the syndrome was related to some aspects of sexual and reproductive history. In particular, the RR in women who had used oral contraceptives (OCs) early (before age 17) reached 11.0 (95% confidence interval [CI] 1.3-97.1) relative to those who had never used OCs. Women who had first intercourse at age 15 or earlier had a 3.3-fold increase in RR (95% CI 1.4-8.0) compared to those who had first intercourse at age 16 or later. CONCLUSION: Our data provide little support for the idea that infection causes the vulvar vestibulitis syndrome. Hormonal factors such as early OC use may be involved in the etiology of this condition.

Adolescent↗

Exercise and obesity.

This paper reviews succinctly the evidence for a role of regular exercise in the prevention and the treatment of obesity and of its metabolic complications. Seventeen propositions relevant to an understanding of the topic are considered. The evidence suggests that regular exercise can be an important factor in the development of sustained negative energy balance conditions provided the volume of activity is high. This implies a program of low to moderate intensity exercise performed on an almost daily basis for at least one hour per session. To induce significant weight and fat losses and to treat overweight and obese patients, compliance to the program for several years becomes a necessity. Exercise increases lipid substrate oxidation and may favor carbohydrate intake for the same amount of energy intake. The acute effects of exercise on resting metabolic rate are well documented, but the long-term influences of exercise training seem to be small and are rapidly suppressed with the cessation of training. The obese benefits also from a regular exercise regimen in terms of improved insulin sensitivity, lipid and lipoprotein profile, and blood pressure, as well as reduced risk of death. Regular exercise, such as walking, is a healthy course of action for the overweight or the obese patients.

Adipose Tissue↗

Non linear weight gain with long term overfeeding in man.

This study deals with the pattern of body weight gain during an overfeeding period with a constant energy intake, in order to assess whether total daily energy expenditure (TEE) increased with body weight and thus could account for the progressive slow down in body weight gain over time. Twenty-four young adult males (12 pairs of identical twins) were overfed by 4.2 MJ per day, six days a week, for a total of 84 days during a 100-day overfeeding period. The total excess amount each man consumed was 353 MJ. It was assumed that, at a given time, the TEE increase (E) was dependent on body weight gain and energy cost (C) was proportional to the daily body weight gain. Results show an exponential increase in body weight, fat free mass, and fat mass (with half-times of 86, 57, and 84 days, respectively) that allows the calculation of E (246 +/- 37 kJ x kg(-1) x d(-1), mean +/- SE) and C (32.3 +/- 2.4 MJ x kg(-1)). Energy expenditure from other sources besides resting metabolic rate, such as physical activity and thermic effect of food, may represent as much as 65% of E. At the beginning of the overfeeding period, almost all the energy surplus was recovered as body substances but this proportion decreased to 60% after 100 days of overfeeding. It is concluded that 1) TEE changes were related to body weight change, 2) about 65% of E were accounted for by physical activity, thermic effect of food, or some other components, and 3) the fraction of the energy surplus stored as body substances decreased with the duration of overfeeding.

Adipose Tissue↗

Segregation analysis of body mass index in an unselected French-Canadian sample: the Québec Family Study.

Interest in a single gene etiology for obesity, as assessed by the body mass index (BMI), has been spurred recently by reports of a putative recessive major gene for extreme values, which accounts for as much as 40% of the variance. The major gene hypothesis was evaluated here in the Québec Family Study, a random sample of 375 French-Canadian volunteer families. This report represents one component in a more complete investigation of obesity in these families. In contrast to the recent studies, a major gene hypothesis for BMI was not verified here. Although there was a major effect, it did not conform to a Mendelian pattern of transmission. A multifactorial component (i.e., polygenic and/or common environmental factors) accounted for 42% of the phenotypic variance. In addition, evidence of heterogeneity between the generations was found. The heterogeneity was traced to the major non-Mendelian component (which accounted for 0.01% of the variance in parents and over 40% in offspring) rather than to the multifactorial one. These results would suggest that a simple recessive gene mixed model may not be sufficient to explain the familial distribution of the BMI. Several factors which may have contributed to these results include temporal trends and surrogate effects such as those related to variation in body composition and energy balance components.

Adipose Tissue↗

5-HT3 receptors which modulate [3H]5-HT release in the guinea pig hypothalamus are not autoreceptors.

The 5-HT3 agonist 2-methyl-5-HT had previously been shown to enhance the electrically evoked release of [3H]5-HT from preloaded slices of the guinea pig brain. In the present study, 2-methyl-5-HT (1 microM) was also found to increase the K+ evoked release of [3H]5-HT from preloaded slices of the guinea pig hypothalamus and this effect was blocked by the selective 5-HT3 antagonist ondansetron. In the presence of tetrodotoxin, the enhancement of the K(+)-evoked release of [3H]5-HT by 2-methyl-5-HT in hypothalamus slices was blocked, thus suggesting that the 5-HT3 receptors mediating this effect are not located directly on 5-HT terminals. In agreement with this, 2-methyl-5-HT did not alter the K(+)-evoked release of [3H]5-HT in a synaptosomal preparation of the same brain structure, even at a concentration 10-fold greater than that used in the slices. Taken together, these data indicate that these facilitatory 5-HT3 receptors are not located on 5-HT terminals in the guinea pig hypothalamus and therefore are not autoreceptors.

Animals↗

Genetic influences on energy expenditure in humans.

Variations in human energy expenditure are partly because of an influence of the genotype, even after control for the well-established concomitants of energy expenditure. Using the techniques of genetic epidemiology, we have found that about 40% of the variance in resting metabolic rate, thermic effect of food, and energy cost of low-to-moderate intensity exercise (< or = 5 times the resting metabolic rate) is explained by inherited characteristics. A significant genetic effect has also been reported for the level of habitual physical activity. The existence of a genotype-environment interaction has also been investigated. Thus, in response to chronic overfeeding, as well as negative energy balance, changes in the components of energy expenditure exhibit significant identical twin pair resemblance. Nutrient partitioning is emerging as a major determinant of the individual differences in metabolic rate responses to overfeeding or negative energy balance conditions. Taken as a whole, these observations consistently support the hypothesis that heredity plays a significant role in the various components of energy expenditure in humans.

Adult↗

Sex differences in the relation of visceral adipose tissue accumulation to total body fatness.

The associations between the amount of abdominal adipose tissue (AT) measured by computed tomography (CT) or estimated with predictive equations and the amount of total body fat were compared in samples of 89 men and 75 women. After correction for total body fat mass, men had significantly higher values of visceral AT volume (P < 0.0001) and also higher abdominal visceral AT areas, measured by CT or estimated by predictive equations than women (P < 0.0001). In addition, an increase in total fat mass was associated with a significantly greater increase in visceral AT volume in men than in women (P < 0.0001). In conclusion, these results suggest that the greater health hazards associated with excess fatness in men than in women may be explained by the fact that premenopausal women can accumulate more body fat than men of the same age before reaching the amounts of visceral AT found in men.

Adipose Tissue↗

Abdominal and femoral adipose tissue lipolysis and cardiovascular disease risk factors in men.

The relationships between subcutaneous abdominal and femoral fat cell lipolyses, plasma free-fatty acid (FFA) levels and metabolic variables considered as risk factors for cardiovascular disease (CVD) (plasma glucose, insulin and lipoprotein levels) were investigated in 54 men, aged 36 +/- 3 (SD) years, covering a wide range of body fatness values (body mass indices from 19 to 34 kg m-2). Although there were no consistent relationships between femoral fat cell weight and the metabolic profile, positive and significant associations were found between abdominal fat cell weight and most of the metabolic indices. However, abdominal fat cell lipolysis measured with an alpha 2-(clonidine) or a beta-agonist (isoproterenol) was unrelated to metabolic variables. In contrast, femoral fat cell lipolysis measured in the presence of clonidine was positively associated with fasting plasma insulin, cholesterol (CHOL) and apolipoprotein (apo) B levels, as well as with LDL-CHOL and LDL-apo B concentrations. No association was found between isoproterenol-stimulated lipolysis of femoral adipocytes and the metabolic profile. Comparison of two subgroups of men with either low or high femoral residual lipolysis with clonidine revealed that subjects with the lowest femoral alpha 2-adrenergic component (i.e. the highest residual lipolysis) displayed significant alterations in both plasma lipid-lipoprotein and glucose-insulin levels which could be predictive of an increased risk of CVD. Free fatty acid (FFA) levels measured in the fasting state and during an oral glucose tolerance test (OGTT) were positively associated with fasting plasma insulin and triglyceride levels as well as with both glucose and insulin areas measured during the OGTT. However, regional adipose tissue lipolysis measured in vitro was unrelated to plasma FFA levels. These results support the view that both femoral adipose tissue lipolysis and plasma FFA levels are significant correlates of plasma glucose-insulin homeostasis and lipoprotein-lipid levels, in men. However, as adipose tissue lipolysis and plasma FFA are unrelated to each other, they may be associated with risk variables through independent mechanisms.

Abdomen↗

Functional characterization of a 5-HT3 receptor which modulates the release of 5-HT in the guinea-pig brain.

1. The aims of the present study were to confirm the modulation by 5-HT3 receptors of the electrically evoked release of tritium from slices preloaded with [3H]-5-HT of guinea-pig frontal cortex, hippocampus and hypothalamus, and to assess their functional role in 5-HT release. 2. The selective 5-HT3 agonist, 2-methyl-5-HT, introduced 8 min before the electrical stimulation, enhanced in a concentration-dependent manner the evoked release of [3H]-5-HT in the three brain regions studied. The 5-HT3 agonists, phenylbiguanide and m-chlorophenyl-biguanide, did not enhance the release of tritium in frontal cortex and hypothalamus slices. 3. In hypothalamus slices, this response was lost when 2-methyl-5-HT was introduced 20 min before the stimulation, thus indicating that these 5-HT3 receptors desensitize rapidly. When 2-methyl-5-HT was added 20-min before the first stimulation period to desensitize the 5-HT3 receptors, removed for 24 min, and then re-introduced 8 min before the second stimulation period, the enhancing effect of 2-methyl-5-HT was restored, thus indicating that these 5-HT3 receptors can rapidly regain normal sensitivity. 4. The enhancing effect of 2-methyl-5-HT was attenuated by the 5-HT3 receptor antagonists m-chloro-phenylpiperazine = quipazine = ondansetron > or = ICS 205-930 = BRL 24924 > MDL 72222 = zacopride. 5. The 5-HT reuptake blocker, paroxetine, enhanced the electrically evoked release of tritium when introduced 8 min before stimulation; this effect of paroxetine was blocked by ICS 205-930, thus indicating that these 5-HT3 receptors can be activated by endogenous 5-HT. 6. In the absence of electrical stimulation, 2-methyl-5-HT (10 microM) produced a marked enhancement of the basal release of [3H]-5-HT which was calcium-dependent and blocked by S-zacopride but not by paroxetine. 7. The enhancing effect of 2-methyl-5-HT was dependent both on the frequency of stimulation, as indicated by the attenuated effect of 120 stimulations delivered at 1 Hz instead of 5 Hz, and on the duration of the stimulation, as indicated by the more pronounced effect of pulses delivered at 5 Hz for 24 s instead of 72 s or 120 s.

Animals↗