Véronique Garneau

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.

Association between yogurt consumption, dietary patterns, and cardio-metabolic risk factors

AbstractPurpose To examine whether yogurt consumption is associated with a healthier dietary pattern and with a better cardio-metabolic risk profile among healthy individuals classified on the basis of their body mass index (BMI). MethodsA 91-item food frequency questionnaire, including data on yogurt consumption, was administered to 664 subjects from the INFOGENE study. After principal component analysis, two factors were retained, thus classified as the Prudent and Western dietary patterns.ResultsYogurt was a significant contributor to the Prudent dietary pattern. Moreover, yogurt consumption was associated with lower body weight, waist-to-hip ratio, and waist circumference and tended to be associated with a lower BMI. Consumers had lower levels of fasting total cholesterol and insulin. Consumers of yogurt had a positive Prudent dietary pattern mean score, while the opposite trend was observed in non-consumers of yogurt. Overweight/obese individuals who were consumers of yogurts exhibited a more favorable cardio-metabolic profile characterized by lower plasma triglyceride and insulin levels than non-consumers within the same range of BMI. There was no difference in total yogurt consumption between normal-weight individuals and overweight/obese individuals. However, normal-weight subjects had more daily servings of high-fat yogurt and less daily servings of fat-free yogurt compared to overweight/obese individuals.ConclusionsBeing a significant contributor to the Prudent dietary pattern, yogurt consumption may be associated with healthy eating. Also, yogurt consumption may be associated with lower anthropometric indicators and a more beneficial cardio-metabolic risk profile in overweight/obese individuals.

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 55 years. 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: 2.28 g and 1.69 g, p < 0.0001, total n-3 FA: 2.57 g and 1.99 g, p < 0.0001; respectively). In plasma PL, DPA and DHA percentages were significantly different between men and women (DPA: 1.03% and 0.88%, p < 0.0001, DHA: 3.00% and 3.43%, p = 0.0005; respectively). Moreover, DHA (men: r = 0.52, p < 0.0001; women: r = 0.57, p < 0.0001) and total n-3 FA (men: r = 0.47, p < 0.0001; women: r = 0.52, p < 0.0001) intakes were positively correlated to their respective plasma PL FA levels. In women, EPA (r = 0.44, p < 0.0001) and DPA (r = 0.23, p = 0.02) 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.

Nutrigenomics – perspectives from registered dietitians: a report from the Quebec-wide e-consultation on nutrigenomics among registered dietitians

BACKGROUND Not all healthcare professionals are familiar with nutrigenomics. However, they recognise that nutrigenomics has great potential for the development of preventive health approaches. The present study aimed to provide an overall picture of the current situation about nutrigenomics in the practice of registered dietitians (RDs) from the province of Quebec (Canada). METHODS Three hundred and seventy-three RDs members of the Ordre professionnel des diététistes du Québec completed an online survey that included 34 questions, most of which were closed-ended questions. RESULTS Overall, 76.9% of RDs knew about nutrigenomics. Among RDs with <5 years of experience, 49.2% knew about genetic testing related to nutrition compared to 11.7% for RDs with over 25 years of experience. Currently, 75.9% of RDs working in clinical nutrition in the public sector consider that they do not have the basic knowledge to integrate nutrigenomics in their practice compared to 62.9% for RDs in private practice. When asked about main limitations of genetic testing related to nutrition, RDs considered that genetic testing does not consider the other determinants of health, that genetic testing and their results have poor accuracy, and that there is a lack of scientific evidence. Concerns remained about ethical and legal aspects and its difficult application as a result of poor understanding and/or interpretation by professionals and/or customers. The high costs of these tests were also noted as a limitation. CONCLUSIONS Registered dietitians know and are interested in nutrigenomics, especially those with less experience, although they do not feel adequately qualified to integrate findings from nutrigenomics into their practice.

Genetic contribution to C-reactive protein levels in severe obesity

Obese individuals are characterized by a chronic, low-grade inflammatory state. Increased levels of C-reactive protein (CRP), a marker of inflammation, have been observed in subjects with the metabolic syndrome. We have previously reported that genes encoding proteins involved in the anti-inflammatory and immune response are differentially expressed in visceral adipose tissue of obese men with or without the metabolic syndrome. Among these genes, the interferon-gamma-inducible protein 30 (IFI30), CD163 molecule (CD163), chemokine (C-X-C motif) ligand 9 (CXCL9) and thymic stromal lymphopoietin (TSLP), were selected for further genetic analyses. The aim of the study was to verify whether IFI30, CD163, CXCL9 and TSLP gene polymorphisms contribute to explain the inter-individual variability of the inflammatory profile of obesity assessed by plasma high-sensitivity CRP concentrations. A total of 1185 severely obese individuals were genotyped for single nucleotide polymorphisms (SNPs) covering most of the sequence-derived genetic variability at the IFI30, CD163, CXCL9 and TSLP gene loci (total of 27 SNPs). Following measurement of plasma CRP levels, subjects were divided into two groups, low vs. high using the median value of plasma CRP levels (8.31 mg/L) as a cutoff point. Genotype frequencies were compared between groups. Associations between genotypes and plasma CRP levels (continuous variable) were also tested after adjustments for age, sex, smoking and BMI. The rs11554159 and rs7125 IFI30 SNPs showed a significant difference in genotype frequencies (p<0.05) between subgroups of low vs. high plasma CRP levels (wild type homozygotes: rs11554159=47% vs. 55%, rs7125=31% vs. 24%, for low vs. high CRP groups, respectively). The association between rs11554159 and CRP levels as a continuous variable remained significant (p=0.004). Both carriers of the GA and AA genotypes demonstrated, on average, a 13% lower CRP levels in comparison with GG homozygotes. No association was observed between SNPs in the CD163, CXCL9 and TSLP genes and CRP levels. The IFI30 rs11554159 polymorphism could partially explain the inter-individual variability observed in the inflammatory profile associated with obesity.

Association between Metabolite Profiles, Metabolic Syndrome and Obesity Status

Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW) and overweight/obese (Ov/Ob) individuals, with or without metabolic syndrome (MetS). Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1’s (long chain glycerophospholipids) metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C) and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C) among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine) was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3’s (medium chain acylcarnitines) metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.

Thymic stromal lymphopoietin: an immune cytokine gene associated with the metabolic syndrome and blood pressure in severe obesity.

A previous expression profiling of VAT (visceral adipose tissue) revealed that the TSLP (thymic stromal lymphopoietin) gene was less expressed in severely obese men with (n=7) compared with without (n=7) the MetS (metabolic syndrome). We hypothesized that TSLP SNPs (single nucleotide polymorphisms) are associated with TSLP gene expression in VAT and with MetS phenotypes. Following validation of lower TSLP expression (P=0.003) in VAT of severely obese men and women with (n=70) compared with without (n=60) the MetS, a detailed genetic investigation was performed at the TSLP locus by sequencing its promoter, exons and intron-exon splicing boundaries using DNA of 25 severely obese subjects. Five tagging SNPs were genotyped in the 130 subjects from the expression analysis to test whether these SNPs contributed to TSLP expression variability (ANOVAs) and then genotyped in two independent samples of severely obese men (total, n=389) and women (total, n=894). In a sex-stratified multistage experimental design, ANOVAs were performed to test whether tagging SNPs were associated with MetS components treated as continuous variables. We observed that the non-coding SNP rs2289277 was associated with TSLP mRNA abundance (P=0.04), as well as with SBP [systolic BP (blood pressure)] (P=0.004) and DBP (diastolic BP) (P=0.0003) in men when adjusting for age, waist circumference, smoking and medication treating hypertension. These novel observations suggest that TSLP expression in VAT may partly explain the inter-individual variability for metabolic impairments in the presence of obesity and that specific SNPs (rs2289277 and/or correlating SNPs) may influence TSLP gene expression as well as BP in obese men.

Association between metabolic deteriorations and prior gestational diabetes according to weight status.

The aim of the present study is to investigate the effect of prior gestational diabetes mellitus (GDM) on glucose and insulin homeostasis according to weight status.