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BACKGROUND Recent studies showed that eating behaviors such as disinhibition, emotional and external eating, and snacking mediate genetic susceptibility to obesity. It remains unknown if diet quality and intake of specific food groups also mediate the genetic susceptibility to obesity. OBJECTIVE This study aimed to assess if diet quality and intakes of specific food groups mediate the association between a polygenic risk score (PRS) for body mass index (BMI) and BMI and waist circumference (WC). We hypothesized that poor diet quality, high intakes of energy-dense food groups and low intakes of nutrient-dense food groups mediate the genetic susceptibility to obesity. METHODS This cross-sectional study included 750 participants (56.3% women, age 41.5 ± 14.9 years, BMI 27.8 ± 7.5 kg/m2) from the Quebec Family Study. A PRSBMI based on > 500,000 genetic variants was calculated using LDpred2. Dietary intakes were assessed with a 3-day food record from which a diet quality score (i.e., Nutrient Rich Food Index 6.3) and food groups were derived. Mediation analyses were conducted using a regression-based and bootstrapping approach. RESULTS : The PRSBMI explained 25.7% and 19.8% of the variance in BMI and WC, respectively. The association between PRSBMI and BMI was partly mediated by poor diet quality (β = 0.33 ± 0.12; 95% CI: 0.13, 0.60), high intakes of fat and high-fat foods (β = 0.46 ± 0.16; 95% CI: 0.19, 0.79) and sugar-sweetened beverages (β = 0.25 ± 0.14; 95% CI: 0.05, 0.60), and low intakes of vegetables (β = 0.15 ± 0.08; 95% CI: 0.03, 0.32), fruits (β = 0.37 ± 0.12; 95% CI: 0.17, 0.64) and dairy products (β = 0.17 ± 0.09; 95% CI: 0.02, 0.37). The same trends were observed for WC. CONCLUSIONS The genetic susceptibility to obesity was partly mediated by poor diet quality and intakes of specific food groups. These results suggest that improvement in diet quality may reduce obesity risk among individuals with high genetic susceptibility and emphasize the need to intervene on diet quality among these individuals.

Background and aim Circulating level of glutamate, a by-product of the catabolism of branched-chain amino acids, has been positively correlated with visceral adipose tissue accumulation and waist circumference (WC). The aim of the present study was to assess the potential of using glutamate level to identify individuals with abdominal obesity and a high cardiometabolic risk. Methods and results The study sample included 99 men and 99 women. Fasting serum glutamate was measured using the Biocrates p180 kit. Anthropometric and metabolic variables were used to identify individuals with abdominal obesity (WC ≥ 95 cm in both sexes), the hypertriglyceridemic waist (HTW) phenotype and the metabolic syndrome (MetS). Mean (±SD) age was 34.1 ± 10.1 years, mean BMI was 29.0 ± 6.2 kg/m2 and mean WC was 92.7 ± 16.5 cm. Glutamate was strongly correlated with WC (r = 0.66 for men; r = 0.76 for women, both p Conclusion Glutamate level may represent an interesting potential biomarker of abdominal obesity and metabolic risk.

The glutamate decarboxylase 2 (GAD2) gene encodes for the glutamic acid decarboxylase enzyme (GAD65), which is implicated in the formation of the gamma-aminobutyric acid (GABA), a neurotransmitter involved in the regulation of food intake. The objective of the present study was to test for association between GAD2 single-nucleotide polymorphisms (SNPs) and eating behaviors, dietary intake and obesity in subjects (n=873) from the Quebec Family Study (QFS). Energy and macronutrient intakes were measured using a 3-day dietary record and eating behaviors were assessed using the Three-Factor Eating Questionnaire (TFEQ). Six SNPs capturing about 90% of GAD2 gene variability were genotyped and tested for association with age- and BMI- adjusted phenotypes. No evidence of association was found in men. In women, a SNP (rs992990; c.61450 C>A) was associated with disinhibition (p=0.028), emotional susceptibility to disinhibition (p=0.0005) and susceptibility to hunger (p=0.028). Another SNP (rs7908975; c.8473A>C) was associated with carbohydrate (p=0.021) and lipid (p=0.021) intakes, disinhibition (p=0.011) and two of its subscales (emotional and situational susceptibility) as well as with avoidance of fattening foods (p=0.036). Six-year weight gain was two times higher in women carrying the variants associated with eating behaviors: 4.2kg (vs 2.1kg in non-carriers) in A-allele carriers of c.61450 C>A (p=0.038) and 4.9kg (vs 2.5kg in non-carriers) in C-allele carriers of c. 8473 A>C (p=0.013). The results suggest a role for the GAD2 gene in determining food intake, eating behaviors and weight gain over time in women.

As visceral adipose tissue (AT) accumulation and inflammatory markers are known to increase with age, we examined whether this age-related change in regional AT distribution could contribute to the increase in the concentration of some inflammatory markers found with age. Two hundred eight healthy men aged 18.6 to 72.2 years and covering a wide range of adiposity values (body mass index, 18.5-39.3 kg/m(2)) were studied. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels were measured by enzyme-linked immunosorbent assay. Anthropometric characteristics such as height, weight, and waist girth were measured; and body mass index was calculated. Cross-sectional areas of abdominal AT were obtained at L4-L5 by computed tomography. Fasting blood samples were collected to determine a complete lipoprotein lipid profile, and a 75-g oral glucose tolerance test was performed. Overall, visceral AT accumulation was positively correlated with age (r = 0.51, P.0001) as well as with plasma CRP (r = 0.39, P.0001), IL-6 (r = 0.32, P.0001), and TNF-alpha (r = 0.14, P.05) levels. A significant positive relationship was also observed between age and CRP (r = 0.36, P.0001), IL-6 (r = 0.39, P.0001), or TNF-alpha (r = 0.15, P.05) concentrations. As middle-aged men were characterized by higher CRP (1.32 [25th percentile, 0.71; 75th percentile, 2.71] vs 0.66 [0.36, 1.62] mg/L, P.0001) and IL-6 (1.60 [1.09, 2.28] vs 1.12 [0.77, 1.60] pg/mL, P.0001) levels as well as by a greater amount of visceral AT (P.0001) than young men, we have individually matched 43 young men (age, 28.6 +/- 5.82 years) with 43 middle-aged men (age, 57.6 +/- 5.15 years) on the basis of their visceral AT. Matching for visceral AT eliminated the difference between middle-aged men and younger adult men in inflammatory markers. These results suggest that the age-related variation in CRP and IL-6 is largely explained by differences in visceral AT.

The objective of the present study was to determine the respective contributions of visceral adipose tissue (AT) accumulation and cardiorespiratory fitness to variation of inflammatory markers in men and women. Circulating levels of C-reactive protein, tumor necrosis factor-alpha, interleukin-6, and adiponectin were obtained with visceral AT (computed tomography) and fitness (physical working capacity test) levels in a sample of healthy men (n = 120) and women (n = 152) covering a wide range of adiposity. An inflammation score was developed based on gender-specific percentile values of each inflammatory marker (0 or 1), which yielded a score ranging from 0 (low) to 4 (high). Visceral AT was positively associated with C-reactive protein and interleukin-6 levels (ror =0.35, p0.0001), but negatively associated with adiponectin (r = -0.29, por =0.0003) after adjustment for fitness. After adjusting for visceral AT, fitness was not associated with variation in inflammatory markers in women and only with adiponectin in men (r = -0.20, p = 0.03). In participants with low visceral AT (130 cm(2) for men and100 cm(2) for women), prevalences of participants with an increased inflammation score were 23.9% and 28.0%, respectively, for participants with high and low fitness, whereas in subjects with increased visceral AT, prevalences of a high inflammation score were 60.0% and 61.7%, respectively, for participants with high and low fitness. In conclusion, these results suggest that the previously reported association between poor fitness and low-grade inflammation may be largely attributable to increased visceral AT accumulation and its associated state of insulin resistance, conditions frequently observed in subjects with poor cardiorespiratory fitness.

The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus (QTL) affecting LDL peak particle size (LDL-PPD) and density on the 17q21 region. This region contains the phosphatidylcholine transfer protein gene (PCTP). In the liver, phosphatidylcholine transfer protein binds specifically phosphatidylcholine suggesting a role for this protein in the formation of HDL and possibly VLDL phospholipid membranes.To test the association between two coding polymorphisms (c.29AC (Glu10Ala) and c.188GA (Cys63Tyr)) in PCTP gene and the LDL-PPD.LDL-PPD was measured by non-denaturating 2-16% polyacrylamide gradient gel electrophoresis on 623 QFS subjects.After adjustment for age and sex, carriers of the c.29C allele showed larger LDL-PPD than A/A homozygotes (p0.05). These results remained significant when LDL-PPD was further adjusted for the effects of BMI and triglyceride levels (p0.04). We also observed a three-fold lower risk of having the small (LDL-PPD256A), dense LDL phenotype in subjects carrying the c.29C allele, when compared to A/A homozygotes (OR=0.35 (95% CI: 0.14-0.91; p=0.03)).PCTP gene variants are associated with LDL-PPD.

A genome-wide linkage study was performed to identify chromosomal regions harboring genes influencing lipid and lipoprotein levels. Linkage analyses were conducted for four quantitative lipoprotein/lipid traits, i.e., total cholesterol, triglyceride, HDL-cholesterol (HDL-C), and LDL-C concentrations, in 930 subjects enrolled in the Quebec Family Study. A maximum of 534 pairs of siblings from 292 nuclear families were available. Linkage was tested using both allele-sharing and variance-component linkage methods. The strongest evidence of linkage was found on chromosome 12q14.1 at marker D12S334 for HDL-C, with a logarithm of the odds (LOD) score of 4.06. Chromosomal regions harboring quantitative trait loci (QTLs) for LDL-C included 1q43 (LOD = 2.50), 11q23.2 (LOD = 3.22), 15q26.1 (LOD = 3.11), and 19q13.32 (LOD = 3.59). In the case of triglycerides, three markers located on 2p14, 11p13, and 11q24.1 provided suggestive evidence of linkage (LOD > 1.75). Tests for total cholesterol levels yielded significant evidence of linkage at 15q26.1 and 18q22.3 with the allele-sharing linkage method, but the results were nonsignificant with the variance-component method. In conclusion, this genome scan provides evidence for several QTLs influencing lipid and lipoprotein levels. Promising candidate genes were located in the vicinity of the genomic regions showing evidence of linkage.

Resume L’obesite est une maladie complexe qui resulte d’une interaction entre une multitude de facteurs genetiques et environnementaux. Les progres combines de la genetique quantitative, de la genomique et de la bio-informatique ont permis de mieux comprendre les bases genetiques et moleculaires de l’obesite. Il est maintenant bien etabli que le surplus ponderal et les differentes formes d’obesite sont des conditions qui ont tendance a se concentrer dans les familles. Le risque d’obesite est environ deux a huit fois plus eleve chez un individu presentant des antecedents familiaux comparativement a un individu sans histoire familiale d’obesite, le risque le plus eleve etant observe dans les cas d’obesite massive. L'heritabilite de l’obesite varie en fonction du phenotype a l'etude, et elle tend a etre plus elevee pour les phenotypes relies a la distribution du tissu adipeux (40 a 55 %) que pour les phenotypes qui traduisent l’exces de masse ou de graisse corporelle (5 a 40 %). Le gain de poids et d’adiposite qui surviennent avec l’âge sont egalement influences par l’heredite. L’existence de formes monogeniques d’obesite constitue une preuve que l’obesite peut etre causee par des mutations genetiques, mais seulement 78 cas dus a des mutations au sein de sept genes differents ont ete decrits jusqu’a maintenant. Les formes les plus courantes d’obesite sont sans doute causees par des variations au sein d’un plus grand nombre de genes. Des variations de sequence au sein de 56 genes differents ont ete rapportees comme etant associees a des phenotypes d’obesite, mais seulement dix de ces genes ont montre des resultats positifs dans au moins cinq etudes differentes. En resume, les connaissances actuelles permettent de conclure que les facteurs genetiques peuvent etre impliques dans l’etiologie de l’obesite, et qu’a l’exception de tres rares cas d’obesite severe, les genes en cause sont sans doute des genes qui interagissent avec les facteurs de l’environnement relies a la consommation et a la depense d’energie pour accroitre le risque d’obesite. L’identification de ces genes de susceptibilite est le defi qui attend les chasseurs de genes de l’obesite et des maladies qui lui sont associees au cours de la prochaine decennie.

The objective of the present study was to examine the impact of the T111I missense mutation in exon 3 of the endothelial lipase (EL) gene on HDL and its potential interaction effect with dietary fat. The study sample included 281 women and 216 men aged between 17 and 76 years from the Quebec Family Study. Plasma HDL3-C levels of I111I homozygote women were higher compared with those of women carrying the wild-type allele (P = 0.03). These differences were not attenuated when adjusted for levels of obesity and were not observed among men. Dietary PUFA interacted with the T111I mutation to modulate apolipoprotein A-I (apoA-I) and HDL3-C levels among women. Specifically, a diet rich in PUFA was associated with increased apoA-I levels among women carriers of the I111 allele and with decreased apoA-I among women homozygotes for the wild-type allele (P = 0.002). A similar interaction was observed with plasma HDL3-C levels (P = 0.003). These interactions were not observed among men. In conclusion, the EL T111I mutation appears to have a modest effect on plasma HDL levels. The gene-diet interaction among women, however, suggests that the T111I missense mutation may confer protection against the lowering effect of a high dietary PUFA intake on plasma apoA-I and HDL3-C levels.

The purpose of this study was to assess the association between the international overweight cutoffs for children and youth and coronary heart disease risk factors. The sample included 410 boys and 337 girls 9–18 years of age from the Quebec Family Study. Participants were classified as normal weight or overweight using the international BMI cutoffs, and into normal and elevated risk groups based on the 90th percentile of sex-specific age-adjusted risk factors [blood pressure, fasting total cholesterol (CHOL), LDL-C, HDL-C, CHOL/HDL-C, triglycerides, glucose, and physical work capacity]. Overweight participants had between 1.6 and 9.1 times the risk of elevated risk factors compared to normal-weight participants. Further, boys and girls with four or more risk factors were 19 and 43 times more likely to be overweight, respectively, compared to participants with no risk factors. The results add evidence that the international cutoffs are related to health risks in youth, supporting the adoption of the guidelines.

The stability of indicators of the metabolic syndrome from childhood and adolescence to young adulthood was examined. The sample included 76 males and 71 females measured between the ages of 8 and 18 years and again as young adults (12 year follow-up). Indicators included the sum of three trunk skinfolds (SF3), mean blood pressure (MBP), and fasting blood glucose (GLY), high-density lipoprotein cholesterol (HDL-C), ratio of total cholesterol to HDL-C (CHOL/HDL), and triglycerides (TG). The indicators were subjected to principal components analysis to obtain a composite risk factor index (RFI). Partial interage correlations, controlling for initial age and length of follow-up, were 0.70 and 0.50 for SF3, 0.40 and 0.54 for MBP, 0.58 and 0.56 for HDL-C, 0.51 and 0.57 for CHOL/HDL, 0.37 and 0.20 (NS) for TG, 0.30 and 0.14 (NS) for GLY, and 0.51 and 0.46 for the RFI, in males and females, respectively. The results indicate that indicators of the metabolic syndrome are moderately stable from childhood and adolescence into young adulthood.

Background. The purpose of the study was to examine the 7-year stability of systolic (SBP) and diastolic (DBP) blood pressures in the Canadian population. Methods. The sample included 1,503 participants 7–69 years of age from the 1981 Canada Fitness Survey who were remeasured in Campbell's Survey of 1988. Both SBP and DBP were adjusted for the effects of body mass index (BMI) using regression procedures. Results. Interage correlations from baseline to follow-up ranged from −0.17 to 0.61 for SBP and from −0.22 to 0.51 for DBP. With few exceptions, correlations were positive and significant, and were highest and most consistent in adulthood. Further, between 27 and 39% of participants in the upper or lower quintiles in 1981 remained there in 1988. There were few differences in adiposity between those who remained in the upper or lower quintiles and those who did not. One exception was that males who remained in the upper quintile of SBP had greater values for BMI, sum of skinfolds, and waist circumference at baseline. Among adults, the best predictor of future blood pressure was baseline blood pressure, which accounted for between 12 and 34% of the variance in follow-up blood pressure, followed by age, follow-up BMI, and, in females, baseline physical activity levels. Conclusions. Blood pressure demonstrated low to moderate stability over 7 years in Canada, and baseline level of adiposity was related to the stability of SBP in males.

The gene-gene interactions between markers in the alpha2-, beta2-, and beta3-adrenergic receptor (ADR) genes and obesity-related phenotypes were studied in the Quebec Family Study (QFS) cohort. The prevalence of the Arg allele of the Arg16Gly polymorphism in the beta2-ADR gene was higher (49%) in males with a body mass index (BMI) of 35 kg/m2 or higher versus those with a BMI less than 35 kg/m2 (33%; P = .010). The beta2-ADR gene Arg16Gly and Gln27Glu polymorphisms were associated with plasma total and low-density lipoprotein (LDL) cholesterol concentrations. In addition, the homozygotes for the 6.3-kb allele of DraI polymorphism in the alpha2-ADR gene had the lowest mean abdominal subcutaneous fat area (P = .012) and total fat area (P = .003), as well as insulin area, under the curve during an oral glucose tolerance test ([OGTT] P = .004). Several ADR gene-gene interaction effects on abdominal fat distribution and plasma lipids were detected. First, significant interactions between alpha2- and beta3-ADR genes were observed on total (P = .015) and subcutaneous (P = .004) abdominal fat. Second, interaction effects between alpha2- and beta2-ADR gene variants influenced total, high-density lipoprotein (HDL), and LDL cholesterol concentrations. Finally, there were interactions between markers within the beta2-ADR gene affecting plasma triglyceride concentrations and subcutaneous abdominal fat. From these results, we conclude that polymorphisms in the ADR genes contribute to body fat and plasma lipid variability in men. Gene-gene interactions among the ADR genes contribute to the phenotypic variability in abdominal obesity and plasma lipid and lipoprotein, but not in visceral fat levels.

Glycerol kinase (GK) represents the primary entry of glycerol into glucose and triglyceride metabolism. Impaired glucose tolerance (IGT) and hypertriglyceridemia are associated with an increased risk of diabetes mellitus and cardiovascular disease. The relationship between glycerol and the risk of IGT, however, is poorly understood. We therefore undertook the study of fasting plasma glycerol levels in a cohort of 1,056 unrelated men and women of French-Canadian descent. Family screening in the initial cohort identified 18 men from five families with severe hyperglycerolemia (values above 2.0 mmol/liter) and demonstrated an X-linked pattern of inheritance. Linkage analysis of the data from 12 microsatellite markers surrounding the Xp21.3 GK gene resulted in a peak LOD score of 3.46, centered around marker DXS8039. In addition, since all of the families originated in a population with a proven founder effect-the Saguenay Lac-St.-Jean region of Quebec-a common disease haplotype was sought. Indeed, a six-marker haplotype extending over a region of 5.5 cM was observed in all families. Resequencing of the GK gene in family members led to the discovery of a N288D missense mutation in exon 10, which resulted in the substitution of a highly conserved asparagine residue by a negatively charged aspartic acid. Although patients with the N288D mutation suffered from severe hyperglycerolemia, they were apparently otherwise healthy. The phenotypic analysis of the family members, however, showed that glycerol levels correlated with impaired glucose metabolism and body-fat distribution. We subsequently noted a substantial variation in glycerolemia in subjects of the initial cohort with normal plasma glycerol levels and demonstrated that this variance showed significant family resemblance. These results suggest a potentially important genetic connection between fasting glycerolemia and glucose homeostasis, not only in this X-linked deficiency but, potentially, in individuals within the "normal" range of plasma glycerol concentrations.

The familial etiology of the response in total fat mass (FM) and abdominal visceral fat (AVF) to 20 weeks of exercise training was investigated in families participating in the HERITAGE Family Study. AVF (measured by computed tomographic scanning) and FM (measured by underwater weighing techniques) were assessed at baseline (in a sedentary state) and after 20 weeks of exercise training. The response AVF (AVFdelta) and response FM (FMdelta) were computed as the simple delta values (posttraining - baseline) and adjusted for the effects of sex, generation, and a polynomial in age using multiple regression analysis. To index the AVF response independently of the response in FM and the initial level of visceral fat, the AVFdelta was also adjusted for age and baseline AVF (AVFB) and FMdelta. Familial correlation analysis was used to investigate the multifactorial familial effects (polygenic and/or familial environmental), and segregation analysis was used to search for major gene effects. For the age-adjusted AVFdelta, a putative recessive locus accounting for 18% of the variance (q2 = 1%) was detected. Adjusting AVFdelta for AVFB and FMdelta slightly increased the percentage of variance accounted for (to 26%, q2 = 3%) but did not radically alter the pattern of the parameter estimates. For FMdelta, a putative dominant locus accounting for 31% of the variance (q2 = 49%) was noted. In conclusion, the results were consistent across methods in suggesting that there is little evidence of a multifactorial heritability for either AVFdelta or FMdelta. Rather, the familial etiology of the response to exercise training appears to be primarily due to putative major genes (a recessive locus for AVFdelta and a dominant locus for FMdelta). In addition, a pleiotropic/oligogenic system underlying these variables was inferred. That is, the putative loci for FMdelta and/or AVFB also may impact the AVFdelta, with an additional independent major locus effect on AVFdelta after the former influences have been removed.

A major gene hypothesis for heparin releasable plasma lipoprotein lipase (PH-LPL) activity was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of Caucasian descent who participated in the HERITAGE Family Study. Segregation analyses were performed on PH-LPL adjusted for age, and on PH-LPL activity adjusted for age and fasting insulin. Prior to adjustment for insulin, neither a major gene effect nor a multifactorial component could be rejected, and support for a major gene was equivocal i.e. neither the Mendelian transmission nor the no transmission (equal tau s) models were rejected. However, after adjusting for the effects of insulin, a major gene effect on PH-LPL activity was unambiguous. The putative locus accounted for 60% of the total phenotypic variance, and the homozygous recessive form affected 10% (q2) of the sample (i.e. gene frequency (q) = 0.31), and led to a low PH-LPL value. The lack of a significant multifactorial effect suggested that the familial etiology of PH-LPL activity adjusted for insulin was likely to be primarily a function of the major locus. In conclusion, the present study is the first to report segregation analyses on PH-LPL activity prior to and after adjusting for insulin, and suggests that there is an indication of a pleiotropic genetic effect on PH-LPL activity and insulin, in addition to a major gene effect on PH-LPL activity alone.

Background: The prevention of obesity appears to be a better approach than treatment; thus, the prediction of future obesity from current status is important. Objective: The aim of the study was to examine the stability of adiposity and adipose tissue distribution (ATD) in the Canadian population. Design: The sample included 1048 males and 1063 females aged 7-69 y at baseline from the Campbell's Survey, a 7-y follow-up of the Canada Fitness Survey. Indicators of adiposity included body mass index (BMI), sum of 5 skinfold thicknesses (SF5), and waist circumference (Waist), whereas indicators of ATD included the ratio of trunk to extremity skinfold thicknesses adjusted for SF5 (TER adj ), and Waist adjusted for BMI (Waist adj ). Results: Interage correlations ranged from 0.53 to 0.91 for BMI, from -0.09 to 0.72 for SF5, from 0.24 to 0.89 for Waist, from 0.23 to 0.73 for TER adj , and from 0.18 to 0.77 for Waist adj . Correlations for BMI were higher than for SF5, suggesting that fat-free mass may contribute to the stability of BMI. Although lower than those for BMI, correlations for indicators of ATD were significant, indicating a propensity to retain an android or gynoid pattern. Furthermore, the average percentage of participants remaining in the lower or upper quintiles for the various indicators ranged from 37.8% to 66.7% in males and from 47.0% to 65.3% in females, indicating that those in the lower and upper portions of the distribution tend to remain there. Conclusion: Obesity and ATD showed significant stability over 7 y in the Canadian population.

The purpose of this study was to investigate the importance of familial aggregation in abdominal visceral fat (AVF) level as assessed by computed tomography (CT). Four measures of abdominal adipose tissue, obtained from an abdominal scan between the fourth and fifth Lumbar vertebrae (L4-L5) taken in 366 adult subjects from 100 French-Canadian nuclear families, were considered in this study. Total abdominal fat, AVF, subcutaneous abdominal fat, obtained by computing the difference between total and AVF tissue areas, and the visceral to total abdominal fat ratio were measured. Spouses, parent-offspring, and sibling correlations were computed by maximum likelihood methods after adjustment of the four phenotypes for age and for age and total fat mass (FM) derived from underwater weighing. Significant familial aggregation was found for all phenotypes, whether adjusted or not for body FM. However, after adjustment of data for body FM, in addition to age, all spouse correlations became nonsignificant, suggesting that the familial aggregation of abdominal fat is primarily genetic. Heritability estimates reached 42% and 56% for subcutaneous fat and AVF, respectively. These results suggest that genetic factors are major determinants of the familial aggregation observed in the amount of abdominal fat, irrespective of total body fat content, and that AVF seems more influenced by genetic factors than abdominal subcutaneous adipose tissue. These findings imply that some individuals are more at risk than others to exhibit the various metabolic complications associated with upper-body obesity because of their inherited tendency to store abdominal fat in the visceral depot rather than in the subcutaneous depot.

Six pairs of male monozygotic (MZ) twins were submitted to a 22-day overfeeding period during which they ingested a daily surplus of 1,000 kcal above their individual daily energy needs in the form of a mixed diet. Serum lipids, lipoproteins, and apoprotein A and B concentrations were measured before and after the overfeeding period. Percentage of body fat, fasting plasma glucose, and insulin levels as well as plasma glucose and insulin concentrations after a glucose challenge were also measured before and after overfeeding. Results showed that before overfeeding, MZ twins exhibited a significant intrapair resemblance for total serum cholesterol (CHOL), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and for the high density lipoprotein-cholesterol/total cholesterol ratio (HDL-CCHOL) (8.2 ≦ F ratios ≦ 32.7, P < .01). The overfeeding experiment induced significant increases only in serum CHOL (P < .01) and in serum LDL-C (P < .05). However, although mean group values of serum TG, HDL-C, and HDL-CCHOL ratio were not significantly modified by overfeeding, there were large interindividual variations in the response of these variables to the experiment. Results suggest that changes in serum TG, HDL-C, and in the HDL-CCHOL ratio were significantly associated with the genotype of the subjects as a significant intrapair resemblance in the response to overfeeding was observed for these variables (0.69 ≦ r ≦ .85, P < .05). Moreover, individual changes in serum HDL-C and in HDL-CCHOL ratio were negatively correlated with changes in serum TG (r = −.64, P < .05 and r = −.84, P < .01; respectively). Finally, subjects that showed an increase in serum TG levels during overfeeding also demonstrated elevated fasting plasma insulin concentrations (r = .67, P < .05) and increased plasma insulin levels during an oral glucose challenge (r = .68; P < .05). These results suggest that the genotype may determine the sensitivity to develop hypertriglyceridemia and a potentially atherogenic lipoprotein-lipid profile (reduced HDL-CCHOL ratio) following a short-term caloric excess. These results also suggest that heredity plays a role in the interindividual variation observed in plasma lipoproteins when chronically overfed.

ABSTRACF Total energy intake and intakes of carbohydrate, fat, and protein as well as the percentage ofenergy derived from these nutrients were calculated from a 3-d dietary record in 1597 subjects living in 375 families ofFrench descent. Familial correlations were computed in pairs of biological relatives and relatives by adoption and used in the path-analysis BETA model to determine the contribution of genetic and nongenetic factors in the familial resemblance observed in energy intake. No significant genetic effect was found for intake of any nutrient tested (h2 � 1 1%) and cultural inheritance was found to be more important than genetic inheritance. Nontransmitted environmental factors, including home environmental effects, were found to account for more than 50% ofthe variation observed in the energy-intake components. These results suggest that the average genetic influence on nutrient intake is negligible and that nongenetic effects associated mainly with home environmental effects are the major affecters ofenergy intake. Am J Clin Nutr l988;47:629-35.

Submaximal power output and body fatness have been measured in 1307 subjects recruited from 375 families coming from an area of 80 km around Quebec city. Total energy, carbohydrate, sugar, fat, saturated fat and alcohol intakes were calculated from a 3-day dietary record. The association between dietary intakes and the indicators of physical fitness was studied in adults (n=727) and children (n=580) of both sexes. Correlation analyses with residuals of age performed in each generation and sex subsample showed that body fatness is significantly but negatively associated with all intakes (−0.16≤r≤−0.50), with the exception of alcohol intake. On the other hand, multiple correlations of all intakes on submaximal power output range from 0.26 to 0.30 in adults, and from 0.20 to 0.24 in children. These observations suggest that submaximal power output is less related to energy intakes and that the association tends to be slightly more important in adults than in children. These data support the contention that physical fitness is determined by the genotype and the habitual energy expenditure and to a lesser degree by the nutritional habits.

The relationships between body fatness, fat distribution and blood pressure (BP) were studied in 234 women and 238 men, aged 18–50 years. In both sexes, subcutaneous (s.c.) fat (assessed by the measurement of s.c. skinfolds) and percent body fat (measured by underwater weighing) were correlated significantly with diastolic (0.27 ⩽ r ⩽ 0.37, p Analysis of variance (2 × 2 factorial with fixed effects) confirmed that, in men, the distribution of s.c. body fat was, per se, associated with diastolic BP (F = 8.43, p