Annie Bouchard-Mercier

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

The metabolic signature associated with the Western dietary pattern: a cross-sectional study

BackgroundMetabolic profiles have been shown to be associated to obesity status and insulin sensitivity. Dietary intakes influence metabolic pathways and therefore, different dietary patterns may relate to modifications in metabolic signatures. The objective was to verify associations between dietary patterns and metabolic profiles composed of amino acids (AAs) and acylcarnitines (ACs).Methods210 participants were recruited in the greater Quebec City area between September 2009 and December 2011. Dietary patterns had been previously derived using principal component analysis (PCA). The Prudent dietary pattern was characterised by higher intakes of vegetables, fruits, whole grain products, non-hydrogenated fat and lower intakes of refined grain products, whereas the Western dietary pattern was associated with higher intakes of refined grain products, desserts, sweets and processed meats. Targeted metabolites were quantified in 37 participants with the Biocrates Absolute IDQ p150 (Biocrates Life Sciences AG, Austria) mass spectrometry method (including 14 amino acids and 41 acylcarnitines).ResultsPCA analysis with metabolites including AAs and ACs revealed two main components explaining the most variance in overall data (13.8%). PC1 was composed mostly of medium- to long-chain ACs (C16:2, C14:2, C14:2-OH, C16, C14:1-OH, C14:1, C10:2, C5-DC/C6-OH, C12, C18:2, C10, C4:1-DC/C6, C8:1 and C2) whereas PC2 included certain AAs and short-chain ACs (xLeu, Met, Arg, Phe, Pro, Orn, His, C0, C3, C4 and C5). The Western dietary pattern correlated negatively with PC1 and positively with PC2 (r = −0.34, p = 0.05 and r = 0.38, p = 0.03, respectively), independently of age, sex and BMI.ConclusionThese findings suggest that the Western dietary pattern is associated with a specific metabolite signature characterized by increased levels of AAs including branched-chain AAs (BCAAs) and short-chain ACs.Trial registrationNCT01343342

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.

Effects of peroxisome proliferator-activated receptors, dietary fat intakes and gene-diet interactions on peak particle diameters of low-density lipoproteins.

The risk of cardiovascular diseases (CVDs) is modulated by gene–diet interactions. The objective of this study was to examine whether gene–diet interactions affect peak particle diameters (PPD) of low-density lipoprotein (LDL). Methods: The study included 674 participants. A food frequency questionnaire was administered to obtain dietary information. LDL-PPD was determined by non-denaturing 2–16% polyacrylamide gradient gel electrophoresis. Peroxisome proliferator-activated receptor (PPAR) gene polymorphisms PPARα L162V (rs1800206), PPARγ P12A (rs1801282) and PPARδ –87T→C (rs2016520) were determined by PCR-RFLP. Results: Among carriers of thePPARα L162V polymorphism, gene–diet interaction effects on LDL-PPD were observed with saturated fat (p = 0.0005) and total dietary fat (p = 0.006). Among PPARα V162 carriers, subjects with higher saturated fat intakes had smaller LDL-PPD than those with lower intakes (254.23 ± 2.74 vs. 256.21 ± 2.61 Å, respectively, p = 0.007). Among subjects homozygous for the PPARα L162 allele, those with higher saturated fat intakes had larger LDL-PPD than those with lower saturated fat intakes (255.86 ± 2.66 vs. 255.05 ± 2.65 Å, respectively, p = 0.01). Gene–diet interactions were also found for PPARγ P12A polymorphism with saturated fat intake (p = 0.04) and for PPARδ –87T→C with the polyunsaturated/saturated fat ratio (p = 0.0013). Conclusions: These results stress that dietary factors should be included in studies determining the effect of different polymorphisms on CVD risk factors.

Polymorphisms, de novo lipogenesis, and plasma triglyceride response following fish oil supplementation

Interindividual variability in the response of plasma triglyceride concentrations (TG) following fish oil consumption has been observed. Our objective was to examine the associations between single-nucleotide polymorphisms (SNPs) within genes encoding proteins involved in de novo lipogenesis and the relative change in plasma TG levels following a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid. SNPs within SREBF1, ACLY, and ACACA genes were genotyped using TAQMAN methodology. After correction for multiple comparison, only two SNPs, rs8071753 (ACLY) and rs1714987 (ACACA), were associated with the relative change in plasma TG concentrations (P = 0.004 and P = 0.005, respectively). These two SNPs explained 7.73% of the variance in plasma TG relative change following fish oil consumption. Genotype frequencies of rs8071753 according to the TG response groups (responders versus nonresponders) were different (P = 0.02). We conclude that the presence of certain SNPs within genes, such as ACLY and ACACA, encoding proteins involved in de novo lipogenesis seem to influence the plasma TG response following fish oil consumption.

Polymorphisms in Genes Involved in Fatty Acid β-Oxidation Interact with Dietary Fat Intakes to Modulate the Plasma TG Response to a Fish Oil Supplementation

A large inter-individual variability in the plasma triglyceride (TG) response to an omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs) within genes involved in fatty acid β-oxidation and dietary fat intakes. Two hundred and eight (208) participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g EPA and 1.1 g DHA). Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187) and ACOX1 (rs17583163) genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid β-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation.

Associations between dietary patterns and LDL peak particle diameter: a cross-sectional study.

Objective: Dietary patterns are used to evaluate the effects of overall nutritional habits on health status, and low-density lipoprotein–peak particle diameter (LDL-PPD) has been recognized as an emerging risk factor for cardiovascular disease (CVD). The aim of this study is to verify whether an association exists between dietary patterns and LDL-PPD. Methods: A total of 635 participants aged between 18 and 55 years were included in this cross-sectional study. Nutritional information was collected with a validated food frequency questionnaire. To establish dietary patterns, factor analysis was performed, which led to characterization of the Western and Prudent dietary patterns. Nondenaturing 2%–16% polyacrylamide gradient gel electrophoresis was used to characterize LDL-PPD. Results: The Western pattern was characterized by high consumption of food such as refined grains, French fries, and red meats, and the Prudent pattern by nonhydrogenated fat, vegetables, eggs, and fish. For the Western profile, a negative correlation was found between score value and LDL-PPD before (r = −0.082, p = 0.039) and after adjustment for age (r = −0.080, p = 0.043). A negative correlation between scores for the Prudent profile and the LDL-PPD adjusted for age, sex, plasma triglycerides, and energy was observed (r = −0.12204, p = 0.0021). After division by tertiles and adjustment for the confounding effects of age, sex, plasma triglyceride levels, and energy, a significant difference (p = 0.0015) in LDL-PPD was noted between the highest tertile (255.21 ± 3.61 Å) and the lowest tertile (255.79 ± 3.68 Å) of the Prudent pattern. Conclusions: Dietary patterns, such as the Western and the Prudent, are associated with LDL-PPD. Dietary patterns can be used to assess the effects of nutritional habits on health status.

Genome-Wide Association Study of Dietary Pattern Scores

Dietary patterns, representing global food supplies rather than specific nutrients or food intakes, have been associated with cardiovascular disease (CVD) incidence and mortality. The contribution of genetic factors in the determination of food intakes, preferences and dietary patterns has been previously established. The current study aimed to identify novel genetic factors associated with reported dietary pattern scores. Reported dietary patterns scores were derived from reported dietary intakes for the preceding month and were obtained through a food frequency questionnaire and genome-wide association study (GWAS) conducted in a study sample of 141 individuals. Reported Prudent and Western dietary patterns demonstrated nominal associations (p < 1 × 10−5) with 78 and 27 single nucleotide polymorphisms (SNPs), respectively. Among these, SNPs annotated to genes previously associated with neurological disorders, CVD risk factors and obesity were identified. Further assessment of SNPs demonstrated an impact on gene expression levels in blood for SNPs located within/near BCKDHB (p = 0.02) and the hypothalamic glucosensor PFKFB3 (p = 0.0004) genes, potentially mediated through an impact on the binding of transcription factors (TFs). Overrepresentations of glucose/energy homeostasis and hormone response TFs were also observed from SNP-surrounding sequences. Results from the current GWAS study suggest an interplay of genes involved in the metabolic response to dietary patterns on obesity, glucose metabolism and food-induced response in the brain in the adoption of dietary patterns.