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 (3 g/d). Six subjects did not lower their plasma TG (+9 %) levels (non-responders) and were matched to 6 subjects who lowered TG (−41 %) 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

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 Canada’s 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

Les effets de l'âge, du sexe, de l'indice de masse corporelle et du génotype de l'APOE sur les facteurs de risque cardiovasculaires suite à une supplémentation en acides gras polyinsaturés oméga-3

Ce projet d’intervention nutritionnelle avait pour but d’étudier la variabilité interindividuelle observée dans la réponse métabolique des facteurs de risque des maladies cardiovasculaires (MCV) à une supplémentation en acides gras polyinsaturées (AGPI) oméga-3 (n-3). Deux-cent dix participants (97 hommes et 113 femmes) ont complété la période de supplémentation de 6 semaines avec cinq grammes d’huile de poisson, dont 3 grammes d’oméga-3 par jour (1.9 à 2.2g EPA + 1.1g DHA). Suite à l’intervention, une diminution significative des niveaux de triglycérides (TG) sanguins a été observée. De plus, les résultats de cette étude suggèrent que l’âge, le sexe, l’indice de masse corporelle (IMC) et le génotype de l’APOE peuvent être identifiés comme étant des facteurs importants de la modulation des concentrations plasmatiques des facteurs de risque de MCV suite à une supplémentation en AGPI n-3.The goal of this nutritional intervention was to test the interindividual variability observed in the metabolic response to an omega-3 (n-3) polyunsaturated fatty acids (PUFA) supplementation. Two hundred and ten subjects (97 men and 113 women) completed the intervention. A supplementation with five grams of fish oil, providing 3 grams of n-3 per day (1.9 to 2.2g EPA + 1.1g DHA) has been administered for a 6-week period following a 2-week run-in period where nutritional recommendations were established. After the intervention, a significant decrease in blood triglyceride (TG) levels was observed. In addition, the results of this study suggest that age, sex, body mass index, and APOE genotype may be identified as potential contributions to important cardiovascular disease risk factors in response to an n-3 PUFA supplementation

Polymorphisms in Fatty Acid Desaturase (FADS) Gene Cluster: Effects on Glycemic Controls Following an Omega-3 Polyunsaturated Fatty Acids (PUFA) Supplementation

Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity (HOMA-IS) and serum fatty acid composition. Objective: To investigate whether common genetic variations in the FADS gene cluster influence fasting glucose (FG) and fasting insulin (FI) responses following a 6-week n-3 polyunsaturated fatty acids (PUFA) supplementation. Methods: 210 subjects completed a 2-week run-in period followed by a 6-week supplementation with 5 g/d of fish oil (providing 1.9 g–2.2 g of EPA + 1.1 g of DHA). Genotyping of 18 SNPs of the FADS gene cluster covering 90% of all common genetic variations (minor allele frequency ≥ 0.03) was performed. Results: Carriers of the minor allele for rs482548 (FADS2) had increased plasma FG levels after the n-3 PUFA supplementation in a model adjusted for FG levels at baseline, age, sex, and BMI. A significant genotype*supplementation interaction effect on FG levels was observed for rs482548 (p = 0.008). For FI levels, a genotype effect was observed with one SNP (rs174456). For HOMA-IS, several genotype*supplementation interaction effects were observed for rs7394871, rs174602, rs174570, rs7482316 and rs482548 (p = 0.03, p = 0.01, p = 0.03, p = 0.05 and p = 0.07; respectively). Conclusion: Results suggest that SNPs in the FADS gene cluster may modulate plasma FG, FI and HOMA-IS levels in response to n-3 PUFA supplementation

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

Purpose 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). Methods A 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. Results Yogurt 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. Conclusions Being 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

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

Transcriptomic and metabolomic signatures of an n-3 polyunsaturated fatty acids 2 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 Canada's 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