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C Bouchard

Publications and source records attributed to C Bouchard.

At least 55 records · Page 3Linked to original sources

The human obesity gene map: the 2000 update.

This report constitutes the seventh update of the human obesity gene map incorporating published results up to the end of October 2000. Evidence from the rodent and human obesity cases caused by single-gene mutations, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci uncovered in human genome-wide scans and in cross-breeding experiments in various animal models, and association and linkage studies with candidate genes and other markers are reviewed. Forty-seven human cases of obesity caused by single-gene mutations in six different genes have been reported in the literature to date. Twenty-four Mendelian disorders exhibiting obesity as one of their clinical manifestations have now been mapped. The number of different quantitative trait loci reported from animal models currently reaches 115. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 130 studies reporting positive associations with 48 candidate genes. Finally, 59 loci have been linked to obesity indicators in genomic scans and other linkage study designs. The obesity gene map reveals that putative loci affecting obesity-related phenotypes can be found on all chromosomes except chromosome Y. A total of 54 new loci have been added to the map in the past 12 months and the number of genes, markers, and chromosomal regions that have been associated or linked with human obesity phenotypes is now above 250. Likewise, the number of negative studies, which are only partially reviewed here, is also on the rise.

Animals↗

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not associated with training-induced changes in body composition: The HERITAGE Family Study.

OBJECTIVE: To investigate the association between the Trp64Arg polymorphism of the beta3-adrenergic receptor gene and changes in body composition in response to endurance training. RESEARCH METHODS AND PROCEDURES: Adult sedentary white and black subjects participating in the HERITAGE Family Study were measured before and after 20 weeks on endurance training for the body mass index, fat mass, percentage of body fat, fat-free mass, sum of eight skinfolds, and subcutaneous, visceral, and total abdominal fat areas. The association between the Trp64Arg polymorphism and the response phenotypes, computed as the difference between pre- and post-training values, was tested by analysis of covariance separately in men and women. The gene by race interaction term was also tested. RESULTS: No race differences were observed for allelic and genotype frequencies. Training resulted in significant reduction of body fat in both men and women. No association of the Trp64Arg polymorphism was observed with training-induced changes for any of the body composition phenotypes in both men and women. DISCUSSION: These results suggest that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not related to changes in body composition in response to exercise training.

Adipose Tissue↗

Stability of adiposity phenotypes from childhood and adolescence into young adulthood with contribution of parental measures.

OBJECTIVE: The stability of several indicators of body composition and adipose tissue distribution over 12 years was quantified. RESEARCH METHODS AND PROCEDURES: The participants were 77 boys and 76 girls who were evaluated along with their parents at baseline as children and adolescents (8 to 18 years of age) and remeasured as young adults 12 years later. Indicators of body composition included the body mass index, fat mass, fat free mass, percentage of body fat, sum of six skinfolds (SF6), and the first principal component of six age-adjusted skinfold residuals. Relative adipose tissue distribution was represented by the second principal component of skinfold residuals and a trunk-to-extremity skinfold ratio, adjusted for SF6. RESULTS: Partial interage correlations, controlling for initial age and length of follow-up, were 0.65 and 0.59 for the body mass index, 0.59 and 0.64 for fat mass, 0.65 and 0.57 for fat free mass, 0.50 and 0.57 for percentage of body fat, 0.66 and 0.44 for SF6, 0.64 and 0.42 for the first principal component of six age-adjusted skinfold residuals, 0.19 and 0.31 for the second principal component of skinfold residuals, and 0.41 and 0.47 for trunk-to-extremity skinfold ratio, adjusted for SF6, in men and women, respectively. Multiple regression analyses indicated that the significant partial R(2) values of parental measurements on the prediction of their offspring in young adulthood ranged from 2% to 9%. DISCUSSION: The results indicate moderately high stability of indicators of body composition and somewhat lower stability of measures of adipose tissue distribution. Overall, parental measures offer less predictive value than do measures of childhood and adolescent body composition and adipose tissue distribution.

Adipose Tissue↗

Genetic variation at the uncoupling protein 1, 2 and 3 loci and the response to long-term overfeeding.

OBJECTIVE: To evaluate the effects of uncoupling protein (UCP) 1, UCP2 and UCP3 gene variants on body composition and metabolic changes in response to chronic overfeeding and the recovery after the period of overfeeding. SUBJECTS AND DESIGN: Twenty-four normal weight men (21+/-2 y), who constituted 12 pairs of identical twins, ate a 4.2 MJ/day energy surplus, 6 days a week, during a period of 100 days. The subjects were asked to return to the laboratory for testing at 4 months and for a final examination 5 y after completion of the overfeeding protocol. METHODS: Resting metabolic rate (RMR) measurements were performed before and after overfeeding. A 4.2 MJ test meal was consumed, after which calorimetric measurements were continued for 240 min. Total body fat was assessed by hydrodensitometry and total subcutaneous fat by the sum of eight skinfolds. Polymorphisms were typed by PCR and PCR-RFLP-techniques. Thyroid stimulating hormone (TSH) concentrations after a thyrotropin releasing hormone (TRH) injection were measured by radioimmunoassay (RIA). RESULTS: The changes in body weight and adiposity were not different between UCP1 Bcl I, UCP2 alanine to valine (A55V), UCP2 insertion/deletion (I/D) or UCP3 Rsa I genotypes. However, the recovery from overfeeding was worse among G-allele carriers of the UCP1 Bcl I, I allele non-carriers of the UCP2 I/D, AV heterozygote subjects of the UCP2 A55V and CC subjects of the UCP3 Rsa I polymorphisms. RMR was lower both before (P=0.01) and after (P=0.001) overfeeding in subjects with the CC genotype of the UCP3 Rsa I polymorphism. Moreover, after overfeeding, the UCP2 A55V heterozygote and UCP3 Rsa I CC homozygote subjects had significantly higher respiratory quotient (RQ) values at rest (P<0.01) and during the meal test (P from<0.01 to<0.05). Also mean plasma TSH concentrations 20, 30 and 45 min after the TRH injection increased more with overfeeding among UCP2 A55V (P<0.005) and UCP3 Rsa I CC (P=0.017) subjects. CONCLUSIONS: These data suggest that UCP polymorphisms may play a role in the recovery from the overfeeding by regulating substrate oxidation in response to long-term caloric surplus. The association of the UCP2 A55V and UCP3 Rsa I CC genotypes with a greater increase in the TSH response to TRH load could reflect a compensatory mechanism counteracting the effects of overfeeding. A longer period of exposure to chronic positive energy balance conditions may be necessary before sequence variation in UCP2 and UCP3 makes an impact on thyroid metabolism to influence body mass and composition changes.

Adult↗

Impact of high-intensity exercise on energy expenditure, lipid oxidation and body fatness.

OBJECTIVE: Two studies were conducted to assess the potential of an increase in exercise intensity to alter energy and lipid metabolism and body fatness under conditions mimicking real life. METHODS: Study 1 was based on the comparison of adiposity markers obtained in 352 male healthy adults who participated in the Québec Family Study who either regularly participated in high-intensity physical activities or did not. Study 2 was designed to determine the effects of high-intensity exercise on post-exercise post-prandial energy and lipid metabolism as well as the contribution of beta-adrenergic stimulation to such differences under a real-life setting. RESULTS: Results from Study 1 showed that men who regularly take part in intense physical activities display lower fat percentage and subcutaneous adiposity than men who never perform such activities, and this was true even if the latter group reported a lower energy intake (917 kJ/day, P<0.05). In Study 2, the high-intensity exercise stimulus produced a greater post-exercise post-prandial oxygen consumption as well as fat oxidation than the resting session, an effect which disappeared with the addition of propranolol. In addition, the increase in post-prandial oxygen consumption observed after the high-intensity exercise session was also significantly greater than that promoted by the low-intensity exercise session. CONCLUSION: These results suggest that high-intensity exercise favors a lesser body fat deposition which might be related to an increase in post-exercise energy metabolism that is mediated by beta-adrenergic stimulation.

Adipose Tissue↗

A new gene related to human obesity identified by suppression subtractive hybridization.

OBJECTIVE: The aim of the research was to identify genes specially expressed in the obese state and potentially involved in the pathogenesis of obesity. DESIGN AND SUBJECTS: We used the technique of suppression subtractive hybridization (SSH), which combines subtractive hybridization with PCR, to generate a population of PCR fragments enriched for transcripts of high or low abundance from differentially expressed genes. PolyA+ mRNA was isolated from subcutaneous abdominal adipose tissue of five massively obese (>35 kg/m(2)) and five normal-weight (<25 kg/m(2)) women. cDNA generated from RNA pooled from the obese subjects was contrasted by SSH with an excess of pooled cDNA from the normal-weight women. RESULTS: Seventy-nine clones were obtained among which one showed by RT-PCR a higher expression in obese than in normal-weight subjects. This gene was shown to be predominantly expressed in adipose tissue in contrast to brain, liver, kidney, heart and skeletal muscle, and was called "Adipogene". No expression was detected in lung, pancreas and placenta. The cDNA was 1.5 kb long with an open reading frame of 1004 nucleotides encoding a protein of 334 amino acids (37 kDa). No significant sequence similarity was found in databanks, except for weak amino acid homologies with prokaryotic AraC/XylS transcriptional regulator family. Adipogene is encoded on chromosome 8, less than 1 centiMorgan (cM) from the beta3 adrenergic receptor (ADRB3) locus. Weak linkages were observed with body mass index (BMI) and three microsatellite markers located within 10 cM of Adipogene, whereas no linkage was observed with Trp64Arg ADRB3 polymorphism using the Québec Family Study database. CONCLUSION: Using the SSH technique, we have identified a new gene, called Adipogene, which is overexpressed in the adipose tissue of the obese individuals and could be involved in obesity.

Adipose Tissue↗

Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women.

OBJECTIVE: Leptin is an adipocyte-secreted hormone involved in body weight regulation, acting through the leptin receptor, localised centrally in the hypothalamus as well as peripherally, amongst others on adipose tissue. The aim of this study was to evaluate whether polymorphisms in the leptin receptor (LEPR) gene were related to obesity and body fat distribution phenotypes, such as waist and hip circumferences and the amount of visceral and subcutaneous fat. METHODS: Three known LEPR polymorphisms, Lys109Arg, Gln223Arg and Lys656Asn, were typed on genomic DNA of 280 overweight and obese women (body mass index (BMI)>25), aged 18-60 y. General linear model (GLM) analyses were performed in 198 pre- and 82 postmenopausal women, adjusting the data for age and menopausal state, plus fat mass for the fat distribution phenotypes. RESULTS: No associations were found between the LEPR polymorphisms and BMI or fat mass. In postmenopausal women, carriers of the Asn656 allele had increased hip circumference (P=0.03), total abdominal fat (P=0.03) and subcutaneous fat (P=0.04) measured by CT scan. Total abdominal fat was also higher in Gln223Gln homozygotes (P=0.04). Also in postmenopausal women, leptin levels were higher in Lys109Lys homozygotes (P=0.02). CONCLUSION: In conclusion, polymorphisms in the leptin receptor gene are associated with levels of abdominal fat in postmenopausal overweight women. Since body fat distribution variables were adjusted for fat mass, these results suggest that DNA sequence variations in the leptin receptor gene play a role in fat topography and may be involved in the predisposition to abdominal obesity.

Adipose Tissue↗

Interactions among the glucocorticoid receptor, lipoprotein lipase and adrenergic receptor genes and abdominal fat in the Québec Family Study.

OBJECTIVE: To investigate whether interactions between glucocorticoid receptor (GRL), lipoprotein lipase (LPL) and adrenergic receptor (ADR) gene markers contribute to individual differences in indicators of adiposity and abdominal obesity, including visceral fat level. DESIGN AND SUBJECTS: Cross-sectional study; 742 individuals from the phase 2 of the Québec Family Study cohort. MEASUREMENTS: Total body fat assessed by hydrodensitometry and the sum of six skinfolds. Abdominal fat areas measured by computed tomography and adjusted for age, sex and total fat mass in all analyses. GRL Bcl I, alpha 2A-ADR Dra I and beta 2-ADR Ban I markers were typed by Southern blot, and other markers by polymerase chain reaction technique. RESULTS: It is confirmed that the 4.5 kb allele of the GRL BclI polymorphism is associated with a higher amount of abdominal visceral fat (AVF) depot (P for trend<0.001) independent of the level of total body fat. Furthermore, the alpha 2-ADR Dra I variant is associated with lower cross-sectional areas of abdominal total (P=0.003) and subcutaneous (P=0.012) adipose tissue. Gene-gene interactions between GRL and alpha 2-ADR genes affecting overall adiposity (P=0.016) as well as between GRL and beta 2-ADR genes (P=0.049) having influence on total abdominal fat levels were observed. When the three genes were considered together in the same analysis, significant interactions having influence on overall adiposity (P=0.017), abdominal total (P=0.032) and visceral fat (P=0.002) were observed. About 1-2% of the total variation in total fatness and abdominal fat was explained by these gene-gene interactions. CONCLUSION: There is an association between the GRL BclI polymorphism and increased AVF levels independent of the level of total body fat. The alpha 2-ADR DraI variant is associated with a lower cross-sectional area of abdominal total fat. Numerous interactions between GRL and ADR markers on overall adiposity and total abdominal fat as well as between GRL, LPL and ADR genes on overall adiposity, abdominal total and visceral fat suggest that the genetic architecture of body fat content and adipose tissue distribution is complex although some genes, like GRL, may have ubiquitous effects.

Adipose Tissue↗

Beta-2 adrenergic receptor variants are associated with subcutaneous fat accumulation in response to long-term overfeeding.

OBJECTIVE: The effects of alpha-2A (A2A)-, beta-2 (B2)- and beta-3 (B3)-adrenergic receptor (ADR) gene polymorphisms on adiposity, fat distribution and plasma insulin and leptin changes in response to long-term overfeeding were explored. METHODS: Twenty four men (mean (+/-s.d.) age 21+/-2 y) who constituted 12 pairs of identical twins ate a 4.2 MJ/day energy surplus, 6 days a week, for a period of 100 days. Total body fat was assessed by hydrodensitometry and total subcutaneous fat by the sum of eight skinfolds. Abdominal fat areas were measured by computerized tomography (CT). Plasma glucose and insulin during fasting and in response to an oral glucose tolerance test (OGTT) were assayed. The insulin and glucose areas were computed using the trapezoidal method. Plasma leptin was measured with an enzyme-linked immunosorbent assay. The ADR polymorphisms were identified by PCR or Southern blot technique. RESULTS: The ADRB2 Gln27Gln genotype (n=10) was associated with a larger gain (percentage change) in weight (P<0.001) and total subcutaneous (P<0.005) fat than the Glu27Glu/Gln27Glu genotype (n=14). In addition, overfeeding induced greater increases in the insulin areas under the curve during the OGTT and the fasting plasma level of leptin (P<0.01 and <0.03, respectively) among Gln27Gln than in the Glu27Glu/Gln27Glu subjects. The body composition and metabolic changes among the ADRB2 BanI 3.7/3.4 kb subjects (n=10) were similar to those of Gln27Gln subjects. ADRA2A DraI (n=4) 6.3/6.3 kb subjects experienced a decrease (-8%) while 6.7/6.3 kb subjects (n=20) registered an increase (+10%; P=0.017) of OGTT glucose area after the 100-day caloric surplus. The four carriers of the ADRB3 variant (Trp64Arg) experienced the same magnitude of changes as the 20 homozygotes for the Trp allele. In general, comparisons based on the 24 subjects considered as unrelated men and the mean values for each of the 12 pairs yielded similar results. CONCLUSION: The ADRB2 Gln27Gln subjects gained more weight and total subcutaneous fatness and also experienced a greater increase in insulin resistance than Glu27Glu/Gln27Glu subjects with exposure to long-term overfeeding. Similar differences were observed between carriers and non-carriers of the ADRB2 3.7/3.4 kb BanI variant. Genetic variation at the ADRB2 locus could thus be one of the factors responsible for the large inter-individual differences observed in the response to long-term alterations in energy balance and should be further investigated.

Abdomen↗

Polymorphism in exon 6 of the dopamine D(2) receptor gene (DRD2) is associated with elevated blood pressure and personality disorders in men.

A deficient dopamine D(2) receptor (DA2) formation or action may contribute to hypertension via an increase of catecholamine release. In addition, Axis II personality disorders that appears odd or eccentric (cluster A) is associated with a low density of DA2. This study sought to examine if a NcoI restriction fragment length polymorphism (C to T transition) in exon 6 of the dopamine D(2) receptor gene (DRD2) was associated with these characteristics. The genotypes (CC, CT and TT) were compared in anthropometric, endocrine, metabolic and haemodynamic variables as well as estimates of personality disorders in 284 randomly selected 51-year-old men. Homozygotes for the C allele constituted 49% of the men and homozygotes for the T allele 9%, while heterozygotes were 41%. The TT genotype was associated with elevated systolic and diastolic blood pressure, independent of obesity and endocrine abnormalities, including the hypothalamic-pituitary-adrenal axis regulation. Moreover, the TT genotype was significantly more frequent among subjects with grade 1 (mild) hypertension (>140/90 mm Hg) compared to normotensive subjects (<130/85 mm Hg). The polymorphism in exon 6 of the DRD2 was also significantly associated with cluster A personality disorders. These results suggest that a polymorphism in exon 6 of the DRD2examined with the restriction enzyme NcoI is associated with an elevated blood pressure, independent of obesity. Paranoid or schizoid personality disorders is also associated with a polymorphism of the DRD2, which might be associated with a previously demonstrated low density of this receptor.

Alleles↗

Interactions among the glucocorticoid receptor, lipoprotein lipase, and adrenergic receptor genes and plasma insulin and lipid levels in the Quebec Family Study.

The aim of the study was to investigate the possible interactions among the glucocorticoid receptor (GRL), lipoprotein lipase (LPL), and adrenergic receptor (ADR) genes on plasma insulin and lipid levels. The study was cross-sectional and based on 742 individuals from phase 2 of the Quebec Family Study (QFS) cohort. Gene markers were identified by Southern blot analysis or polymerase chain reaction (PCR). Plasma glucose and insulin in the fasted state and during an oral glucose tolerance test (OGTT) were determined and insulin and glucose areas were computed. Triglyceride (TG) and cholesterol concentrations in plasma and lipoprotein fractions were determined enzymatically. The results show that GRL and LPL variants had independent effects on plasma high-density lipoprotein cholesterol (HDL-C) and two beta2-ADR variants were related to total cholesterol concentrations. The alpha2-ADR gene Dral polymorphism was the only variant that had an independent effect on the plasma insulin area. Gene-gene interaction effects were found between GRL and alpha2-ADR genes for low-density lipoprotein cholesterol ([LDL-C] P = .013) and between GRL and LPL genes for HDL-C (P = .045). Higher-order interaction effects involving GRL, LPL, and ADR markers were observed for the plasma insulin area (P = .001 to .025) but not the glucose area. After correction for multiple tests, the findings remained essentially unchanged for the insulin area but became nonsignificant for the lipid phenotypes. In conclusion, multiple interactions among GRL, LPL, and ADR gene markers contribute to insulin metabolism and perhaps to lipid levels, while no significant effect is found for each gene separately. The LPL locus appears to determine the pattern of interactions with ADR and GRL loci. These results suggest that gene-gene interaction effects could play a role in the etiology of risk factors for common chronic diseases.

Area Under Curve↗

Changes in blood lipids consequent to aerobic exercise training related to changes in body fatness and aerobic fitness.

The contribution of changes in body fatness and aerobic fitness to changes in blood lipids after aerobic exercise training was investigated. The sample included 295 men (77 black, 218 white) and 355 women (131 black, 224 white), aged 17 to 65 years, from the HERITAGE Family Study. Participants underwent measurements at baseline and after 20 weeks of supervised exercise training on a cycle ergometer. Body fat mass (FM, in kilograms) was determined by underwater weighing, and aerobic fitness (maximal oxygen uptake, VO(2max), in milliliters per minute) was assessed by cycle ergometry. Blood lipid measurements included fasting plasma levels of high-density lipoprotein cholesterol (HDL-C), HDL(2)-C, HDL(3)-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (CHOL), CHOL/HDL, and triglycerides (TG). A composite lipid change index (LCI) was derived by subjecting the Delta scores for the individual blood lipids to principal components analysis. The exercise training was accompanied by a mean increase of 17.5% in VO(2max) and a mean decrease of 3.3% in FM. Partial correlations, controlled for age, between absolute changes in VO(2max) and changes in the blood lipids were consistently low and nonsignificant. On the other hand, absolute changes in FM were significantly (P <.05) associated with changes in HDL-C (r = -.23), HDL(2)-C (r = -.17), and CHOL/HDL (r =.24) and the LCI (r = -.27) in men and with changes in LDL-C (r =.22), CHOL (r =.19), and CHOL/HDL (r =.15) and the LCI (r = -.19) in women. Forward stepwise regression confirmed that the change in FM was a better predictor of changes in blood lipids than the change in VO(2max), entering as a predictor in 4 of 8 regressions in both men and women. Change in VO(2max) did not enter as a significant predictor in any regression. Further, there were no differences in LCI between the upper and lower quartiles of VO(2max) change. On the other hand, there were significant differences between the low and high quartiles of FM change. No race effects were observed in any of the relationships, except that race was a significant predictor of changes in TG in both men and women. In conclusion, changes in blood lipids associated with aerobic exercise training do not appear to be related to changes in aerobic fitness per se; rather, they are weakly to moderately associated with changes in body fatness.

Adipose Tissue↗

Race differences in the pattern of familial aggregation for dehydroepiandrosterone sulfate and its responsiveness to training in the HERITAGE Family Study.

Using a familial correlation model to assess familial influences, baseline dehydroepiandrosterone sulfate (DHEAS) and its change (post-training minus baseline) in response to a 20-week endurance exercise training program were analyzed in 85 black families who participated in the HERITAGE Family Study (HERITAGE). Baseline levels were adjusted for a polynomial in age, and the training response was adjusted for a polynomial in age, as well as the baseline values, within 4 sex-by-generation groups before genetic analysis. We found that the maximal heritability for baseline DHEAS reached 66% (with no sex and generation differences) in black families, which is slightly (but not significantly) higher than the estimate (58%) reported previously in 99 white families in HERITAGE. Whereas weak, but significant, familial effects (26%) for the training response were previously reported for whites in HERITAGE, they were undetectable in the present study. Furthermore, we found heterogeneity in the pattern of familial aggregation (primarily due to different spouse and parent-offspring correlations) for both the baseline and its training response between blacks and whites. In conclusion, baseline DHEAS levels in blacks were also determined by substantial familial factors (just as for whites), independent of the effects of age and sex. Genetic and nongenetic familial components influencing baseline DHEAS levels in both races may be different.

Adolescent↗

A polymorphism in the regulatory region of the corticotropin-releasing hormone gene in relation to cortisol secretion, obesity, and gene-gene interaction.

In recent years, a considerable body of evidence has emerged regarding the pathogenic role of cortisol in abdominal obesity. The regulation of the corticotropin-releasing hormone (CRH) gene might play an essential role because it is the primary hypothalamic neuropeptide involved in the control of adrenal secretion of cortisol. Therefore, we examined the hypothalamic-pituitary-adrenal function by repeated salivary samples for the assessment of cortisol as well as other endocrine, anthropometric, metabolic, and circulatory variables in middle-aged Swedish men (n = 284). With the restriction enzyme XmnI, a variant in the 5'-flanking region of the CRH gene was identified (T255G). The observed genotype frequencies were 89.9% and 9.7% for T/T and T/G, respectively. Only 1 subject was homozygous for the rare allele (0.4%; G/G). The results showed that the XmnI polymorphism of the CRH gene is not associated with an altered cortisol-secretory pattern or sensitivity to glucocorticoids or with obesity and its related metabolic and circulatory perturbations. However, when the interaction effect between a previously described TthlllI glucocorticoid-receptor gene polymorphism and the present XmnI CRH polymorphism was investigated, the cortisol levels before and during physiologic stress and the total diurnal cortisol secretion were significantly increased among subjects who were carriers for both variants. From these results, we conclude that an abnormal production rate of the CRH gene product in the presence of an inadequate glucocorticoid receptor density might lead to elevated cortisol levels.

Aging↗

Relationship of changes in maximal and submaximal aerobic fitness to changes in cardiovascular disease and non-insulin-dependent diabetes mellitus risk factors with endurance training: the HERITAGE Family Study.

The purpose of this study was to determine the relationship between changes in maximal oxygen uptake (VO2 max) and submaximal markers of aerobic fitness and changes in risk factors for cardiovascular disease (CVD) and non-insulin-dependent diabetes mellitus (NIDDM) consequent to a 20-week endurance training program. The 502 participants in this study were healthy and previously sedentary men (n = 250) and women (n = 252) of varying age (17 to 65 years) and race (blacks n = 142; whites n = 360) who had completed the HERITAGE Family Study testing and training protocol. Following baseline measurements, participants trained on cycle ergometers 3 days/week for a total of 60 exercise sessions starting at the heart rate (HR) associated with 55% of VO2 max for 30 minutes/session. This was progressively increased to the HR associated with 75% of VO2 max for 50 minutes/session, which was maintained during the last 6 weeks. VO2 max, heart rate at 50 W, power output at 60% of VO2 max, lipids and lipoproteins, resting blood pressure, body composition including abdominal fat (computed tomography [CT] scan), and blood glucose and insulin at rest and at peak following an intravenous glucose tolerance test (IVGTT) were determined both before and after training. Following training, there were significant increases in VO2 max (16%) and the power output at 60% of VO2 max and a significant decrease in HR at 50 W. These changes in markers of aerobic fitness were significantly correlated only to the changes in the body composition variables and the lipids and lipoproteins. Further, there was considerable individual variation in response for all variables studied. Finally, when risk factor data were analyzed by quartile of change in VO2 max, there were few significant relationships. It is concluded that there is a significant relationship between changes in markers of aerobic fitness and changes in several risk factors for CVD and NIDDM. However, the magnitude of these relationships is small.

Adolescent↗

Genome-wide linkage scan to detect loci influencing levels of dehydroepiandrosterones in the HERITAGE Family Study.

A genome-wide linkage scan was performed to identify genomic regions that influence levels of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and DHEA fatty acid esters (DHEA-FA) at baseline and in response to 20 weeks of endurance exercise training in sedentary white and black participants in the HERITAGE Family Study. The baseline levels were log-transformed and adjusted for the effects of age and sex prior to genetic analysis. The training responses were adjusted for the effects of age, sex, and the baseline values. A total of 509 autosomal component polymorphic markers were used for the genome scan with an average spacing of 6.0 Mb. Multipoint variance components linkage analyses were performed in nuclear families containing 360 white and 106 black sibling pairs. We found 5 genomic regions with significant linkages for baseline DHEA-FA in whites, with log odd (LOD) scores over 3.6 (P < 2 x 10(-5)). They include (1) D1S468 (LOD 4.56, 2.533 Mb, 1p36.22); (2) D2S177 (LOD 5.65, 52.663 Mb, 2p16.3); (3) D4S2397 (LOD 3.98, 32.246 Mb, 4p15.2); (4) the paraoxonase loci (LOD 3.93 approximately 3.99, 101.544 approximately 102.933 Mb, 7q21.3), and D7S821 (LOD 3.88, 104.497 Mb, 7q22.1); and (5) D12S372 (LOD 4.66, 2.129 Mb, 12q13.33). In addition, we obtained evidence of suggestive linkages (2.2 < LOD < 3.6; 2 x 10(-5) < P < 7 x 10(-4)) on chromosomes 3p, 6q, and 8q for baseline DHEAS; on chromosomes 2q, 3p, 9q, 10p, 16q, and 17p for baseline DHEA-FA in whites; and on chromosomes 9q and 11p for baseline DHEA in blacks. This is the first genome-wide linkage scan searching for genomic regions influencing human DHEA levels. Several potential candidate genes are located in these genomic regions, which warrant further studies in HERITAGE and other cohorts.

Adult↗

Changes in ventilatory threshold with exercise training in a sedentary population: the HERITAGE Family Study.

UNLABELLED: The purpose of this study was to evaluate the effect of exercise training intensity relative to the ventilatory threshold (VT) on changes in work (watts) and VO2 at the ventilatory threshold and at maximal exercise in previously sedentary participants in the HERITAGE Family Study. We hypothesized that those who exercised below their VT would improve less in VO2 at the ventilatory threshold (VO2vt) and VO2max than those who trained at an intensity greater than their VT. Supervised cycle ergometer training was performed at the 4 participating clinical centers, 3 times a week for 20 weeks. Exercise training progressed from the HR corresponding to 55% VO2max for 30 minutes to the HR associated with 75% VO2max for 50 minutes for the final 6 weeks. VT was determined at baseline and after exercise training using standardized methods. 432 sedentary white and black men (n = 224) and women (n = 208), aged 17 to 65 years, were retrospectively divided into groups based on whether exercise training was initiated below, at, or above VT. RESULTS: 1) Training intensity (relative to VT) accounting for about 26% of the improvement in VO2vt (R2 = 0.26, p < 0.0001). 2) The absolute intensity of training in watts (W) accounted for approximately 56% of the training effect at VT (R2 = 0.56, p < 0.0001) with post-training watts at VT (VT(watts)) being not significantly different than W during training (p > 0.70). 3) Training intensity (relative to VT) had no effect on DeltaVO2max. These data clearly show that as a result of aerobic training both the VO2 and W associated with VT respond and become similar to the absolute intensity of sustained (3 x /week for 50 min) aerobic exercise training. Higher intensities of exercise, relative to VT, result in larger gains in VO2vt but not in VO2max.

Adolescent↗

Evidence for the existence of adaptive thermogenesis during weight loss.

The present study was performed to further investigate the adaptive component of thermogenesis that appears during prolonged energy restriction. Fifteen obese men and twenty obese women underwent a 15-week weight-loss programme. During this programme, body weight and composition as well as resting energy expenditure (REE) were measured at baseline, after 2 and 8 weeks of energy restriction (-2929 kJ/d) and drug therapy (or placebo), and finally 2-4 weeks after the end of the 15-week drug therapy and energy restriction intervention, when subjects were weight stable. Regression equations were established in a control population of the same age. These equations were then used to predict REE in obese men and women at baseline, after 2 and 8 weeks, as well as after the completion of the programme. In both men and women body weight and fat mass were significantly reduced in all cases) while fat-free mass remained unchanged throughout the programme. At baseline, REE predicted from the regression equation was not significantly different from the measured REE in men, while in women the measured REE was 13 % greater than predicted. After 2 weeks of energy restriction, measured REE had fallen by 469 and 635 kJ/d more than predicted and this difference reached 963 and 614 kJ/d by week 8 of treatment in men and women respectively. Once body-weight stability was recovered at the end of the programme, changes in REE remained below predicted changes in men (-622 kJ/d). However, in women changes in predicted and measured REE were no longer different at this time, even if the women were maintaining a reduced body weight. In summary, the present results confirm the existence of adaptive thermogenesis and give objective measurements of this component during weight loss in obese men and women, while they also emphasize that in women this component seems to be essentially explained by the energy restriction.

Adaptation, Physiological↗