Ann-Marie Paradis

The interleukin 6 –174G/C Polymorphism is associated with indices of obesity in men

AbstractObesity represents an expansion of adipose tissue (AT) mass and is closely related to insulin resistance and cardiovascular disease. Several hormonal signals have been shown to originate from AT, one of them being interleukin 6 (IL6), for which one third of circulating levels is accounted for by AT. To study the impact of the IL6 –174G/C polymorphism on obesity-related phenotypes, we genotyped a cohort of 270 French-Canadian men from the greater Quebec City area selected to cover a wide range of body fatness values. The IL6 –174G allele was more commonly observed among lean subjects (body mass index <25kg/m2, χ2 = 7.27, P = 0.007 or waist-line <100cm, χ2 = 6.63, P = 0.01). When men were subdivided according to insulin and glucose levels at 180min following the glucose load, using 160pmol/l and 4.6mmol/l, respectively, as cutoff points, the –174G allele was more frequently observed in groups with low concentrations of either insulin or glucose, P = 0.03 and P = 0.01, respectively. When comparisons between genotype groups were performed, –174G/G homozygotes presented the lowest waist circumference (P < 0.05). In summary, this study showed that, in men, the IL6 –174G/C polymorphism is associated with some indices of body composition and parameters of glucose and insulin homeostasis.

Transcriptomic and metabolomic signatures of an n-3 polyunsaturated fatty acids supplementation in a normolipidemic/normocholesterolemic Caucasian population

OMIC technologies, including transcriptomics and metabolomics, may provide powerful tools for identifying the effects of nutrients on molecular functions and metabolic pathways. The objective was to investigate molecular and metabolic changes following n-3 polyunsaturated fatty acid (PUFA) supplementation in healthy subjects via traditional biomarkers as well as transcriptome and metabolome analyses. Thirteen men and 17 women followed a 2-week run-in period based on Canadas Food Guide and then underwent 6-week supplementation with n-3 PUFA (3 g/day). Traditional biochemical markers such as plasma lipids, inflammatory markers, glycemic parameters and erythrocyte fatty acid concentrations were measured. Changes in gene expression of peripheral blood mononuclear cells were assessed by microarrays, and metabolome profiles were assessed by mass spectrometry assay kit. After supplementation, plasma triglycerides decreased and erythrocyte n-3 PUFA concentrations increased to a similar extent in both genders. Further, plasma high-density lipoprotein cholesterol concentrations and fasting glucose levels increased in women after n-3 PUFA supplementation. N-3 PUFA supplementation changed the expression of 610 genes in men, whereas the expression of 250 genes was altered in women. Pathway analyses indicate changes in gene expression of the nuclear receptor peroxisome proliferator-activated receptor-alpha, nuclear transcription-factor kappaB, oxidative stress and activation of the oxidative stress response mediated by nuclear factor (erythroid-derived 2)-like 2. After n-3 PUFA supplementation, metabolomics profiles demonstrate an increase in acylcarnitines, hexose and leucine in men only and a decrease in saturation of glycerophosphatidylcholine and lysophosphatidylcholine concentrations in all subjects. Overall, traditional and novel biomarkers suggest that n-3 PUFA supplementation exerts cardioprotective effects.

Associations between dietary patterns and gene expression profiles of healthy men and women: a cross-sectional study

BackgroundDiet regulates gene expression profiles by several mechanisms. The objective of this study was to examine gene expression in relation with dietary patterns.MethodsTwo hundred and fifty four participants from the greater Quebec City metropolitan area were recruited. Two hundred and ten participants completed the study protocol. Dietary patterns were derived from a food frequency questionnaire (FFQ) by factor analysis. For 30 participants (in fasting state), RNA was extracted from peripheral blood mononuclear cells (PBMCs) and expression levels of 47,231 mRNA transcripts were assessed using the Illumina Human-6 v3 Expression BeadChips®. Microarray data was pre-processed with Flexarray software and analysed with Ingenuity Pathway Analysis (IPA).ResultsTwo dietary patterns were identified. The Prudent dietary pattern was characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products and the Western dietary pattern, by high intakes of refined grain products, desserts, sweets and processed meats. When individuals with high scores for the Prudent dietary pattern where compared to individuals with low scores, 2,083 transcripts were differentially expressed in men, 1,136 transcripts in women and 59 transcripts were overlapping in men and women. For the Western dietary pattern, 1,021 transcripts were differentially expressed in men with high versus low scores, 1,163 transcripts in women and 23 transcripts were overlapping in men and women. IPA reveals that genes differentially expressed for both patterns were present in networks related to the immune and/or inflammatory response, cancer and cardiovascular diseases.ConclusionGene expression profiles were different according to dietary patterns, which probably modulate the risk of chronic diseases.Trial RegistrationNCT: NCT01343342

Association between Polymorphisms in the Fatty Acid Desaturase Gene Cluster and the Plasma Triacylglycerol Response to an n-3 PUFA Supplementation

Eicosapentaenoic and docosahexaenoic acids have been reported to have a variety of beneficial effects on cardiovascular disease risk factors. However, a large inter-individual variability in the plasma lipid response to an omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation is observed in different studies. Genetic variations may influence plasma lipid responsiveness. The aim of the present study was to examine the effects of a supplementation with n-3 PUFA on the plasma lipid profile in relation to the presence of single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster. A total of 208 subjects from Quebec City area were supplemented with 3 g/day of n-3 PUFA, during six weeks. In a statistical model including the effect of the genotype, the supplementation and the genotype by supplementation interaction, SNP rs174546 was significantly associated (p = 0.02) with plasma triglyceride (TG) levels, pre- and post-supplementation. The n-3 supplementation had an independent effect on plasma TG levels and no significant genotype by supplementation interaction effects were observed. In summary, our data support the notion that the FADS gene cluster is a major determinant of plasma TG levels. SNP rs174546 may be an important SNP associated with plasma TG levels and FADS1 gene expression independently of a nutritional intervention with n-3 PUFA.

Effects of age, sex, body mass index and APOE genotype on cardiovascular biomarker response to an n-3 polyunsaturated fatty acid supplementation.

Objectives: To test whether age, sex, body mass index (BMI), and the apolipoprotein E (APOE) genotype are associated with the metabolic response to an n-3 polyunsaturated fatty acid (PUFA) supplementation. Methods: 210 subjects followed a 2-week run-in period based on Canadas Food Guide and underwent a 6-week 5 g/day fish oil supplementation (1.9 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Cardiovascular disease risk factors were measured. Results: n-3 PUFA supplementation was associated with a decrease of plasma triglyceride levels (p = 0.0002) as well as with an increase of fasting glucose (FG) levels (p = 0.02). Age was associated with post-intervention plasma total cholesterol (p = 0.01), low-density lipoprotein cholesterol (p = 0.007), apolipoprotein B (p = 0.04), and insulin (p = 0.002) levels. Sex was associated with post-intervention plasma high-density lipoprotein cholesterol levels (p = 0.02). BMI was associated with plasma FG (p = 0.02) and insulin levels (p < 0.0001) after the supplementation. APOE genotype was associated with FG (p = 0.001) and C-reactive protein levels (p = 0.03) after the supplementation. Conclusion: Results suggest that age, sex, BMI, and the APOE genotype contribute to the inter-individual variability observed in the metabolic response to an n-3 PUFA supplementation.

Omega-3 fatty acids status in human subjects estimated using a food frequency questionnaire and plasma phospholipids levels

BackgroundIntakes of omega-3 (n-3) fatty acids (FA) are associated with several health benefits. The aim of this study was to verify whether intakes of n-3 FA estimated from a food frequency questionnaire (FFQ) correlate with n-3 FA levels measured in plasma phospholipids (PL).MethodsThe study sample consisted of 200 French-Canadians men and women aged between 18 to 55u2009years. Dietary data were collected using a validated FFQ. Fasting blood samples were collected and the plasma PL FA profile was measured by gas chromatography.ResultsLow intakes of n-3 long-chain FA together with low percentages of n-3 long-chain FA in plasma PL were found in French-Canadian population. Daily intakes of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were similar between men and women. Yet, alpha-linolenic acid (ALA) and total n-3 FA intakes were significantly higher in men compared to women (ALA: 2.28u2009g and 1.69u2009g, pu2009<u20090.0001, total n-3 FA: 2.57u2009g and 1.99u2009g, pu2009<u20090.0001; respectively). In plasma PL, DPA and DHA percentages were significantly different between men and women (DPA: 1.03% and 0.88%, pu2009<u20090.0001, DHA: 3.00% and 3.43%, pu2009=u20090.0005; respectively). Moreover, DHA (men: ru2009=u20090.52, pu2009<u20090.0001; women: ru2009=u20090.57, pu2009<u20090.0001) and total n-3 FA (men: ru2009=u20090.47, pu2009<u20090.0001; women: ru2009=u20090.52, pu2009<u20090.0001) intakes were positively correlated to their respective plasma PL FA levels. In women, EPA (ru2009=u20090.44, pu2009<u20090.0001) and DPA (ru2009=u20090.23, pu2009=u20090.02) intakes were also correlated respectively with EPA and DPA plasma PL FA percentages.ConclusionEstimated n-3 long-chain FA intake among this young and well-educated French-Canadian population is lower than the recommendations. Further, FFQ data is comparable to plasma PL results to estimate DHA and total n-3 FA status in healthy individuals as well as to evaluate the EPA and DPA status in women. Overall, this FFQ could be used as a simple, low-cost tool in future studies to rank n-3 FA status of individuals.

Differences in metabolomic and transcriptomic profiles between responders and non-responders to an n-3 polyunsaturated fatty acids (PUFAs) supplementation

Studies have demonstrated large within-population heterogeneity in plasma triacylglycerol (TG) response to n-3 PUFA supplementation. The objective of the study was to compare metabolomic and transcriptomic profiles of responders and non-responders of an n-3 PUFA supplementation. Thirty subjects completed a 2-week run-in period followed by a 6-week supplementation with n-3 PUFA (3xa0g/d). Six subjects did not lower their plasma TG (+9xa0%) levels (non-responders) and were matched to 6 subjects who lowered TG (−41xa0%) concentrations (responders) after the n-3 PUFA supplementation. Pre-n-3 PUFA supplementation characteristics did not differ between the non-responders and responders except for plasma glucose concentrations. In responders, changes were observed for plasma hexose concentrations, docosahexaenoic acid, stearoyl-CoA-desaturase-18 ratio, and the extent of saturation of glycerophosphatidylcholine after n-3 PUFA supplementation; however, no change in these parameters was observed in non-responders. Transcriptomic profiles after n-3 PUFA supplementation indicate changes in glycerophospholipid metabolism in both subgroups and sphingolipid metabolism in non-responders. Six key genes in lipid metabolism: fatty acid desaturase 2, phospholipase A2 group IVA, arachidonate 15-lipoxygenase, phosphatidylethanolamine N-methyltransferase, monoglyceride lipase, and glycerol-3-phosphate acyltransferase, were expressed in opposing direction between subgroups. In sum, results highlight key differences in lipid metabolism of non-responders compared to responders after an n-3 PUFA supplementation, which may explain the inter-individual variability in plasma TG response.

Dietary patterns and associated lifestyles in individuals with and without familial history of obesity: a cross-sectional study.

BackgroundFamilial history of obesity (FHO) and certain dietary habits are risk factors for obesity. The objectives of this cross-sectional study were 1) to derive dietary patterns using factor analysis in a population of men and women with and without FHO; 2) to compare mean factor scores for each dietary pattern between individuals with and without FHO; and 3) to examine the association between these patterns and anthropometric, lifestyle and sociodemographic variables.MethodsA total of 197 women and 129 men with a body mass index <30 kg/m2 were recruited. A positive FHO (FHO+) was defined as having at least one obese first-degree relative and a negative FHO (FHO-) as no obese first-degree relative. Dietary data were collected from a food frequency questionnaire. Factor analysis was performed to derive dietary patterns. Mean factor scores were compared using general linear model among men and women according to FHO. Regression analyses were performed to study the relationship between anthropometric, lifestyle and sociodemographic variables, and each dietary pattern.ResultsTwo dietary patterns were identified in both men and women : the Western pattern characterized by a higher consumption of red meats, poultry, processed meats, refined grains as well as desserts, and the Prudent pattern characterized by greater intakes of vegetables, fruits, non-hydrogenated fat, and fish and seafood. Similar Western and Prudent factor scores were observed in individual with and without FHO. In men with FHO+, the Western pattern is negatively associated with age and positively associated with physical activity, smoking, and personal income. In women with FHO-, the Prudent pattern is negatively associated with BMI and smoking and these pattern is positively associated with age and physical activity.ConclusionTwo dietary patterns have been identified among men and women with and without FHO. Although that FHO does not seem to influence the adherence to dietary patterns, results of this study suggest that anthropometric, lifestyle and sociodemographic variables associated with dietary patterns differ according to FHO and gender.

Validity of a self-reported measure of familial history of obesity

BackgroundFamilial history information could be useful in clinical practice. However, little is known about the accuracy of self-reported familial history, particularly self-reported familial history of obesity (FHO).MethodsTwo cross-sectional studies were conducted. The aims of study 1 was to compare self-reported and objectively measured weight and height whereas the aims of study 2 were to examine the relationship between the weight and height estimations reported by the study participants and the values provided by their family members as well as the validity of a self-reported measure of FHO. Study 1 was conducted between 2004 and 2006 among 617 subjects and study 2 was conducted in 2006 among 78 participants.ResultsIn both studies, weight and height reported by the participants were significantly correlated with their measured values (study 1: r = 0.98 and 0.98; study 2: r = 0.99 and 0.97 respectively; p < 0.0001). Estimates of weight and height for family members provided by the study participants were strongly correlated with values reported by each family member (r = 0.96 and 0.95, respectively; p < 0.0001). Substantial agreement between the FHO reported by the participants and the one obtained by calculating the BMI of each family members was observed (kappa = 0.72; p < 0.0001). Sensitivity (90.5%), specificity (82.6%), positive (82.6%) and negative (90.5%) predictive values of FHO were very good.ConclusionA self-reported measure of FHO is valid, suggesting that individuals are able to detect the presence or the absence of obesity in their first-degree family members.

Effect of the PPAR-Alpha L162V Polymorphism on the Cardiovascular Disease Risk Factor in Response to n–3 Polyunsaturated Fatty Acids

Background: Dietary n–3 polyunsaturated fatty acids (PUFAs) decrease the risk of cardiovascular disease (CVD). Yet, genetic variations of the gene encoding the peroxisome proliferator-activated receptor-α (PPARα) can also modulate CVD risk factors. Since fatty acids, including n–3 PUFAs, are natural ligands of PPARα, a gene-diet interaction effect could be observed. Aims: To examine whether n–3 PUFA- induced changes in CVD risk factors are influenced by the PPARα L162V polymorphism. Methods: Fourteen men, carriers of the V162 allele and 14 L162 homozygotes, were matched according to age and body mass index. Subjects followed, for 8 weeks, a low-fat diet and then were supplemented daily with 5 g of fish oil for 6 weeks. Results: Baseline characteristics were similar for both genotype groups. Independently of the genotype, the supplementation was associated with a significant decrease in plasma triacylglycerol and fasting glucose concentrations, diastolic blood pressure, and with an increase in total apolipoprotein B concentrations. The extent of the decrease in plasma triacylglycerol concentrations was comparable for both genotype groups (p < 0.03). A significant genotype-by-diet interaction effect was observed for plasma C-reactive protein concentrations (p = 0.01). Conclusions: The PPARα L162V polymorphism may contribute to the interindividual variability in the CVD risk factor response to n–3 PUFAs.