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No abstract is provided for this article.

The glutamate decarboxylase 2 (GAD2) gene encodes for the glutamic acid decarboxylase enzyme (GAD65), which is implicated in the formation of the γ-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.

No abstract is provided for this article.

Biopsies of adipose tissue were obtained from two subcutaneous regions (abdominal and femoral) in a sample of 54 men (32 obese and 22 lean subjects). Clonidine-induced antilipolysis in femoral adipose cells was similar in both groups, whereas subcutaneous abdominal adipocytes of obese individuals showed a higher alpha 2-adrenergic response than did subcutaneous abdominal adipose cells from lean subjects. In addition, epinephrine had a biphasic effect in subcutaneous abdominal adipocytes from obese individuals, as it induced antilipolysis at low concentrations, and a net lipolytic response at higher doses. In contrast, the physiological amine promoted lipolysis in subcutaneous abdominal adipose cells of lean subjects. Epinephrine- and clonidine-induced antilipolysis of subcutaneous abdominal adipocytes was positively associated with the level of subcutaneous abdominal fat measured by computed tomography (CT). Finally, men with a high alpha 2-adrenergic response of subcutaneous abdominal fat cells were fatter than those with a low alpha 2-adrenergic component. These results suggest that, in men with a wide range of body fatness, variations in the lipolytic response of subcutaneous abdominal adipose cells to epinephrine appear to involve changes in the functional balance between alpha 2- and beta-adrenoceptors.

A major gene hypothesis for resting metabolic rate (RMR) was investigated using segregation analysis (POINTER) of data on families participating in Phase 2 of the Québec Family Study. Complete analyses were conducted on RMR adjusted for age, and also on RMR adjusted for age and other covariates, primarily fat mass (FM) and fat‐free mass (FFM). Prior to adjustment for covariates, support for a major gene hypothesis was equivocal — i.e., there was evidence for either a major gene or a multifactorial component (i.e., polygenic and/or familial environment). The multifactorial model was preferred over the major gene model, although the latter did segregate according to Mendelian expectations. However, after the effects of FM and FFM were accounted for, a major gene effect was unambiguous and compelling. The putative locus accounted for 57% of the variance, affected 7% of the sample, and led to high values of RMR. The lack of a significant multifactorial effect suggested that the familial etiology of RMR adjusted for FM and FFM was likely to be entirely a function of the major locus. Comparing the RMR results from pre‐ and post‐adjustment for FM and FFM suggests a plausible hypothesis. We know from earlier studies in this sample that there is a putative major gene for FM and a major non‐Mendelian effect for FFM. The current study leads us to speculate that: (1) the gene(s) affecting body size and body composition also may have an effect on RMR, and further (2) removal of the effect of the major gene(s) for body size and composition allowed for detection of an additional major gene affecting only the RMR. Thus, RMR appears to be an oligogenic trait.

No abstract is provided for this article.

Background. 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 QTL for LDL-peak particle size (LDL-PPD) on the 17q21 region. Three positional candidates were identified in this region according to their implication in the phosphoinositide (PI) cycle: the myotubularin-related protein 4 (MTMR4), the phospholipase C, delta 3 (PLCD3), and the diacylglycerol kinase E (DGKE) genes. Objectives. To test the association between MTMR4, PLCD3, and DGKE gene polymorphisms, LDL-PPD and plasma lipid parameters. Methods. Analyses were performed on 680 subjects of QFS. LDL-PPD was measured by gradient gel electrophoresis on non-denaturating 2–16% polyacrylamide gradient gels. Direct sequencing was performed to identify genetic variations within these genes. Results. The c.-754G>C, c.183G>A, and c.579C>A DGKE SNPs were significantly associated with higher plasma triglyceride levels (p =0.029, p =0.008, p =0.001, respectively). The c.508C>G and c.890T>G MTMR4 polymorphisms were associated with plasma total-cholesterol concentrations (p =0.02, p =0.02, respectively), while no association was observed with PLCD3 gene polymorphisms. Conclusion. The c.579C>A DGKE gene polymorphism is associated with plasma triglyceride levels, while MTMR4 SNPs seem to predict variations in plasma cholesterol levels.

1. Abdominal obesity is associated with numerous metabolic complications. Deep abdominal adipose tissue is critical in the association between the level of abdominal obesity and cardiovascular risk factors. 2. Adipose tissue localization was assessed by computed axial tomography (CAT), and its association with body density and anthropometric measurements was investigated in a sample of fifty-one obese women (percentage body fat 45·9 (SD 5·6)) aged 35·7 (SD 5·5) years. The CAT scans were performed at three levels: lower chest, abdomen and mid-thigh. 3. The total adipose tissue volume computed from these three scans was highly correlated with body fat mass ( r 0·94, P < 0·001). The proportion of deep abdominal fat as measured by the ratio of deep: total adipose tissue areas at the abdominal level was not significantly correlated with body fat mass, but it was moderately associated with the ratio of waist: hip circumferences (WHR) ( r 0·49, P < 0·001). The absolute amount of deep abdominal fat was, however, significantly correlated with body fat mass ( r 0·72, P < 0·001). 4. The subscapular ( r 0·38) and the abdominal ( r 0·38) skinfolds were the only two skinfolds that were significantly associated with the proportion of deep abdominal fat ( P < 0·01). These skinfolds were also those which showed the highest correlation with the absolute amount of deep abdominal fat ( r 0·65, P < 0·001, for both skinfolds). 5. A three-site CAT-scan procedure can be used for the estimation of body fat mass in premenopausal obese women. 6. In these obese women, there was no significant association between total adiposity and the proportion of deep adipose tissue at the abdominal level. 7. In premenopausal obese women, the absolute amount of deep abdominal fat can be predicted from anthropometric measurements with more accuracy than the relative amount of deep abdominal fat.

We investigated the associations between the hepatic lipase gene (LIPC) −514C>T polymorphism and lipases, lipoproteins, and insulin sensitivity (Si) responses to exercise training. Hepatic lipase and lipoprotein lipase activities, plasma lipoprotein levels, and Si were measured in the sedentary state and post–exercise training in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study (n = 662). The LIPC −514C allele frequency was 0.516 (blacks) and 0.796 (whites). Baseline and post–exercise training hepatic lipase activities were 40% higher in CC homozygotes (P < 0.0001) in both races. Black CC homozygotes had lower baseline lipoprotein lipase activity, HDL cholesterol, HDL3, and apolipoprotein (apo)A-1 concentrations. White CC homozygotes had lower baseline HDL cholesterol, apoA-1, LDL cholesterol, and apoB levels that remained low post–exercise training. Baseline Si was not associated with the LIPC genotypes. However, training-induced improvements in Si both in blacks and whites were greater in CC homozygotes (+1.25 ± 0.2 and +0.22 ± 0.2 μU · min−1 · ml−1) than in the TT genotype (+0.27 ± 0.3 and −0.97 ± 0.3 μU · min−1 · ml−1) (P = 0.008 and P = 0.002, respectively). The LIPC −514C allele was associated with higher hepatic lipase activity in sedentary and physically active states and better Si responses to regular exercise both in black and white individuals. The benefits from an exercise program on Si are likely to be substantial in the general population given the high frequency of the LIPC −514C allele, particularly in whites.