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Preterm infants are deficient in long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), a fatty acid (FA) associated with an increase in bronchopulmonary dysplasia (BPD). In two previous randomized control trials, DHA supplementation did not reduce the risk of BPD. We examined the breast milk FA profile, collected 14 days after birth, of mothers who delivered before 29 weeks of gestation and who were supplemented with DHA-rich algae oil or a placebo within 72 h after birth as part of the MOBYDIck trial. Milk FA were analyzed by gas chromatography. The total amount of FA (mg/mL) was similar in both groups but the supplementation increased DHA (expressed as % of total FA, mean ± SD, treatment vs placebo, 0.95 ± 0.44% vs 0.34 ± 0.20%; P

Background: Using a genome-wide association study (GWAS) approach, our group previously computed a genetic risk score (GRS) from single nucleotide polymorphisms (SNPs) of 10 loci that affect the plasma triglyceride (TG) response to an omega-3 (n–3) fatty acid (FA) supplementation. Objectives: The objective was to compute a novel and more refined GRS using fine mapping to include a large number of genetic variants. Methods: A total of 208 participants of the Fatty Acid Sensor (FAS) Study received 5 g fish oil/d, containing 1.9–2.2 g eicosapentaenoic acid and 1.1 g docosahexanoic acid, for 6 wk. Plasma TG concentrations were measured before and after supplementation. Dense genotyping and genotype imputation were used to refine mapping around GWAS hits. A GRS was computed by summing the number of at-risk alleles of tagging SNPs. Analyses were replicated in samples of the FINGEN study. Results: A total of 31 tagging SNPs associated with the TG response were used for GRS calculation in the FAS study. In a general linear model adjusted for age, sex, and body mass index, the GRS explained 49.73% of TG response variance (P < 0.0001). Nonresponders to the n–3 FA supplementation had a higher GRS than did responders. In the FINGEN replication study, the GRS explained 3.67% of TG response variance (P = 0.0006). Conclusions: Fine mapping proved to be effective to refine the previous GRS. Carrying increasing numbers of at-risk alleles of 31 SNPs confers a higher risk of being nonresponsive to n–3 FAs. The genetic profile therefore appears to be an important determinant of the plasma TG response to an n–3 FA supplementation and could be used to target those most likely to gain clinical benefit. This trial was registered at http://www.clinicaltrials.gov as NCT01343342.

Complexities surrounding the manufacture and quality control of nanomedicines become increasingly apparent. This research article offers a case study to investigate how, at the laboratory scale, various stages of liposome and nanoparticle synthesis affect the amount of residual solvent found in the formulations. The objective is to bring insights on the reliability of each of these processes to provide final products which meet regulatory standards and facilitate identifying possible bottleneck early during the development process. The residual solvent at various stages of preparation and purification was measured by headspace gas chromatography. Liposomes were prepared by two different methods with and without solvent. Polymer nanoparticles prepared via nanoprecipitation and purified by ultrafiltration were studied. The effects of purification by size exclusion chromatography and dialysis were also investigated. The complete removal of residual solvent requires processes which go beyond usual preparation methods. This work might prove valuable as a reference for scientists of different fields to compare their own practices and streamline the translation of nanomedicines into efficacious and safe drug products.

Background Diabetes and pregnancy are both associated with oxidative stress, characterized by an increase of F2-isoprostanes from the non-enzymatic oxidation of arachidonic acid, a n − 6 polyunsaturated fatty acid (PUFA). We hypothesized that pregnant women with pre-existing diabetes will be characterized by elevated levels of specific F2-isoPs isomers and altered PUFA composition in plasma early pregnancy when compared to normoglycemic controls. Methods Plasma samples from 23 women with uncomplicated pregnancies and 11 women with pre-existing diabetes in pregnancy were collected between 12 and 18 weeks of pregnancy (MIROS cohort). Six F2-isoprostanes isomers were measured by high-performance liquid chromatography coupled to tandem mass spectrometry. Fatty acids concentrations in plasmatic phospholipids were measured by gas chromatography coupled to a flame ionization detector. Results F2-isoprostanes, specifically the 8-iso-15(R)-PGF2α levels, were 67% higher in diabetic than normoglycemic pregnancies (p = 0.026). The total n − 6 PUFA and arachidonic acid level did not differ between study groups. In contrast, total n − 3 level was 32% lower in diabetic pregnancies than in controls (p = 0.002); EPA(20:5) and DHA(22:6) being specifically reduced (p = 0.035 and p = 0.003 respectively). Delta-6-desaturase (D6D) activity index, calculated using fatty acid ratios, was 9% lower in pre-existing diabetes than in controls (p = 0.042). Conclusions Pre-existing diabetes in early pregnancy displays a distinctive F2-isoprostanes profile when compared to other pathologies of pregnancy, such as preeclampsia, as previously assessed in the same cohort.

This study aimed to determine whether dairy macronutrients alter markers of inflammation and oxidative stress in endothelial cells. Human endothelial cells (HUVEC) were treated with ruminant trans fatty acids (rTFA), either trans-vaccenic acid (tVA) or trans-palmitoleic acid (tPA), whey protein hydrolysate, leucine or combinations of rTFA and dairy protein compounds. Industrial TFA elaidic acid (EA) was also investigated and compared with rTFA. Inflammatory prostaglandins (PG) and F2-isoprostanes (F2-isoP) isomers, markers of oxidative stress, were assessed in cell supernatants by LC-MS/MS. Both tVA and tPA, as well as whey protein hydrolysate, decreased TNFα-induced PG excretion. Combinations of rTFA and dairy protein compounds decreased inflammation to a similar extent than rTFA alone. EA increased class VI F2-isoP isomers, whereas tVA mostly raised class III isomers. In summary, rTFA decreased inflammatory markers and increased oxidative stress markers in endothelial cells. Combinations of rTFA with whey proteins or leucine showed no additive effect.

Dairy products have been hypothesized to protect against type 2 diabetes because of their high content of whey proteins, rich in branched-chain amino acids (BCAAs) - leucine, isoleucine and valine - and lysine, which may decrease postprandial glucose responses and stimulate insulin secretion. Paradoxically, epidemiologic studies also show that higher levels of plasma BCAAs have been linked to insulin resistance and type 2 diabetes. Therefore, the objective was to review the recent clinical evidence concerning the intake of amino acids found in dairy proteins so as to determine their impact on glucose homeostasis in healthy persons and in those with prediabetes and type 2 diabetes. Clinical studies have reported that the major dairy amino acids, namely, leucine, isoleucine, glutamine, phenylalanine, proline and lysine, have beneficial effects on glucose homeostasis. Yet the reported doses of amino acids investigated are too elevated to be reached through adequate dairy product intake. The minor dairy amino acids, arginine and glycine, may improve glucose homeostasis by improving other risk factors for type 2 diabetes. Further, the combination of amino acids may also improve glucose-related outcomes, suggesting additive or synergistic effects. Nevertheless, additional long-term studies in individuals with prediabetes and type 2 diabetes are needed to ascertain the benefits for glucose homeostasis of amino acids found in dairy foods.

Background Omega-3 polyunsaturated fatty acids (n-3 FAs) have several beneficial effects on cardiovascular (CV) disease risk factors. These effects on CV risk profile may be mediated by several factors, including epigenetic modifications. Our objective is to investigate, using genome-wide DNA methylation analyses, methylation changes following an n-3 FA supplementation in overweight and obese subjects and to identify specific biological pathways potentially altered by the supplementation. Results Blood leukocytes genome-wide DNA methylation profiles of 36 overweight and obese subjects before and after a 6-week supplementation with 3 g of n-3 FAs were compared using GenomeStudio software. After supplementation, 308 CpG sites, assigned to 231 genes, were differentially methylated (FDR-corrected Diffscore ≥│13│~ P ≤ 0.05). Using Ingenuity Pathway Analysis system, a total of 55 pathways were significantly overrepresented following supplementation. Among these pathways, 16 were related to inflammatory and immune response, lipid metabolism, type 2 diabetes, and cardiovascular signaling. Changes in methylation levels of CpG sites within AKT3, ATF1, HDAC4, and IGFBP5 were correlated with changes in plasma triglyceride and glucose levels as well as with changes in the ratio of total cholesterol/HDL-cholesterol following the supplementation. Conclusions These data provide key differences in blood leukocytes DNA methylation profiles of subjects following an n-3 FA supplementation, which brings new, potential insights on metabolic pathways underlying the effects of n-3 FAs on CV health. Electronic supplementary material The online version of this article (doi:10.1186/s13148-017-0345-3) contains supplementary material, which is available to authorized users.

Trans fatty acids (TFA) intake has been linked to cardiovascular diseases and liver diseases; yet the effect of TFA on inflammation remains controversial. Accordingly, the objective of this paper was to determine the in vitro effects of TFA on inflammatory gene expression. Human umbilical vein endothelial cells (HUVEC) and human hepatocellular carcinoma (HepG2) cells were treated for 24 h with either trans-vaccenic acid (tVA), trans-palmitoleic acid (tPA) or elaidic acid (EA) at concentrations of 5-150 µM, or with a mixture of tVA and tPA (150/50 µM). All TFA were highly incorporated into cell membranes, as determined by gas chromatography, representing 15-20% of total fatty acids in HUVEC and 3-8% in HepG2 cells. Incorporation of EA, a common industrial TFA, increased the ratio of the stearoyl-CoA desaturase (SCD-1), a key enzyme involved in fatty acid metabolism. Ruminant TFA, including tVA, tPA and the mixture of tVA and tPA, significantly reduced the TNF-α-induced gene expression of TNF, VCAM-1 and SOD2 in HUVEC, as well as TNF and IL-8 in HepG2 cells. EA also decreased inflammatory gene expression in HUVEC, but not in HepG2 cells. The inhibition of peroxisome proliferator-activated receptor (PPAR)-γ did not influence the effects of TFA on gene expression. Overall, physiological and supraphysiological concentrations of TFA, especially tVA and tPA, prevented inflammatory gene expression in vitro. This effect is independent of PPAR-γ activation and may be due to an alteration of fatty acid metabolism in cell membranes caused by the high incorporation of TFA.

A recent review of clinical studies reports that dairy products may improve inflammation, a key etiologic cardiovascular disease risk factor. Yet the impact of dairy proteins on inflammatory markers is controversial and could be mediated by a differential impact of whey proteins and caseins. In this study, we hypothesized that whey proteins may have a greater anti-inflammatory effect than caseins. A model of human umbilical vein endothelial cells, with or without TNF-α stimulation, was used to investigate the effect of several dairy protein compounds on inflammation. Specifically, the impact of whey proteins either isolate or hydrolysate, caseins, and their amino acids on expression of TNF, VCAM-1, SOD2, and eNOS was examined. After a 24-hour incubation period, whey protein hydrolysate, leucine, isoleucine, and valine attenuated the TNF-α-induced endothelial inflammation by normalizing TNF and eNOS gene expression. This effect was not observed in unstimulated cells. Oppositely, caseins, a whey protein/casein mixture (1:4 w/w), and glutamine aggravated the TNF-α-induced TNF and SOD2 gene expression. Yet caseins and whey protein/casein mixture decreased VCAM-1 expression in both unstimulated and stimulated human umbilical vein endothelial cells. Measurement of TNF-α in cell supernatants by immunoassay substantiates gene expression data without reaching statistical significance. Taken together, this study showed that whey proteins and their major amino acids normalize TNF-α-induced proinflammatory gene expression in endothelial cells.

OBJECTIVES: We hypothesized that the intake of industrially originated trans-fatty acids (elaidic acid (EA trans 18: 1n-9)) and ruminant trans fatty acids (trans-palmitoleic acid (TPA t16:1 n-7)) will differentially modify gut microbiota and short-chain fatty acids (SCFA) profiles. The objective is to compare the long- and short-term effects of EA and TPA on the fecal microbiome and SCFAs profiles in mice. METHODS: Forty C57BL/6 mice were divided to 4 groups. Each group was given one of the following 4 formulations in the drinking water: lecithin nanovesicles, nanovesicles containing either lecithin with EA or TPA (86:14 (w/w)) or water alone (control) for 28 days with a normal fat diet. Fecal samples were collected at days 0, 7 and 28. Gut microbiota profiles were determined by 16S rRNA gene sequencing. SCFAs were measured by headspace gas chromatography coupled to a single quadrupole mass spectrometer. Baseline data (relative abundance of bacteria or levels of SCFAs) was pooled and then compared with data from day 7 or day 28 for each formulation. RESULTS: After 7 days of lecithin, 16S rRNA analysis revealed an increase in the relative abundance of Lactobacillus. After 28 days of lecithin, an increase in the relative abundance of Lactobacillus, Erysipelotrichaceae, and Enterobacteriaceae together with a decrease in Bacteroidaceae was observed. Further, a tendency to increase level of butyric acid (P = 0.053) was observed after 28 days of lecithin. After 7 days of EA, an increase in the relative abundance of Lactobacillus, whereas a decrease in the relative abundance of Parabacteroides, Bacteroides, Rumininococcaceae, Lachnospiraceae and Peptococcaceae was observed. After 7 days of TPA, results show a decreased level of isovaleric acid (P = 0.04) and valeric acid (P = 0.03). After 28 days of TPA, data demonstrates an increase in the level of butyric acid (P = 0.01) and propionic acid (P = 0.01). Water intake for 28 days decreased the level of valeric acid (P = 0.02). CONCLUSIONS: Consumption of industrial and ruminant trans-fatty acids modify differentially bacterial taxa present in the gut microbiome and SCFA profiles. FUNDING SOURCES: NSERC, CMDO.

Evidence supports that a high dietary fat intake increases oxidative stress and the risk of diet-induced metabolic disorders such as obesity, diabetes and cardiovascular diseases. F2-isoprostanes (F2-isoP) are formed by the non-enzymatic oxidation of arachidonic acid and are widely used as reliable biomarkers of oxidative stress in clinical studies. Dietary fats may influence F2-isoP levels, as they (1) are metabolic substrates for their formation, (2) modify the lipid composition of tissues, and (3) affect the plasma lipoprotein concentrations which are involved in F2-isoP transport. This review examined the latest clinical evidence on how dietary fats can affect blood circulation and excretion of F2-isoP in individuals with healthy or deteriorated metabolic profiles. Clinical studies reported that saturated or monounsaturated fat-rich diets did not affect F2-isoP levels in adults with healthy or deteriorated metabolic profiles. Though, ω-3 polyunsaturated fatty acids decreased F2-isoP levels in numerous studies, whereas trans-fatty acids raised F2-isoP excretion. Yet, the reported heterogeneous results reveal important considerations, such as the health status of the participants, the biological fluids used to determine F2-isoP, the analytical methods employed and the specific F2-isoP isomers detected. Therefore, future clinical studies should be designed in order to consider these issues in the studies of the effects of fat intake on oxidative stress.

Background: A recent genome-wide association study (GWAS) by our group identified 13 loci associated with the plasma triglyceride (TG) response to omega-3 (n-3) fatty acid (FA) supplementation. This study aimed to test whether single-nucleotide polymorphisms (SNPs) within the IQCJ, NXPH1, PHF17 and MYB genes are associated with the plasma TG response to an n-3 FA supplementation. Methods: A total of 208 subjects followed a 6-week n-3 FA supplementation of 5 g/day of fish oil (1.9-2.2 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Measurements of plasma lipids were made before and after the supplementation. Sixty-seven tagged SNPs were selected to increase the density of markers near GWAS hits. Results: In a repeated model, independent effects of the genotype and the gene-supplementation interaction were associated with plasma TG. Genotype effects were observed with two SNPs of NXPH1, and gene-diet interactions were observed with ten SNPs of IQCJ, four SNPs of NXPH1 and three SNPs of MYB. Positive and negative responders showed different genotype frequencies with nine SNPs of IQCJ, two SNPs of NXPH1 and two SNPs of MYB. Conclusion: Fine mapping in GWAS-associated loci allowed the identification of SNPs partly explaining the large interindividual variability observed in plasma TG levels in response to an n-3 FA supplementation.

Fundamental nutritional studies on bioactive molecules require minimizing exposure to confounding foreign elements, like solvents. Herein, aqueous formulations of lecithin nanovesicles are proposed to study three individual trans fatty acids relevant to human nutrition: elaidic acid, trans-vaccenic acid and trans-palmitoleic acid. This proof-of-concept study describes the encapsulation of fatty acids, in vivo bioavailability, and the use of nanovesicles in behavioral experiments. The oral bioavailability of the encapsulated molecules and the selective exposure of animals to each trans-fatty acid of interest were confirmed in healthy rats. Behavioral studies also evidenced that nanovesicles can be used to evaluate the palatability of the lipids and investigate food preferences in mice. Altogether this study shows that lecithin nanovesicles offer an elegant tool to efficiently deliver hydrophobic molecules to animal models. This approach paves the way for future studies deconvoluting the nutritional effects of trans-fatty acids.

Dairy product intake is inversely associated with the risk of type 2 diabetes (T2D) in numerous cohort studies; yet, the beneficial effects of increased dairy product intake on T2D risk factors such as fasting plasma glucose, fasting insulin, insulin resistance with the homeostasis model assessment, and glycated hemoglobin (HbA1c) remain inconclusive in clinical trials. The objective of this study was to systematically review clinical trials observing the effects of elevated compared with minimal intake of dairy products on T2D risk factors in subjects without diabetes. Five databases [Medline, EMBASE, Central, CINAHL, AMED (Allied and Complementary Medicine)] were searched to identify randomized controlled trials that used elevated quantities of dairy products from ruminant sources in comparison with a lower intake in control groups. The review outcomes were fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HbA1c. Risk of bias and quality of evidence according to Grading of Recommendations Assessment, Development, and Evaluation were addressed. From the 10,627 citations screened, 44 studies (3016 participants) were included, 38 of which were used in the meta-analyses. Fasting glucose was positively associated with elevated dairy intake [34 studies, n = 2678; mean difference (MD): 0.07 mmol/L; 95% CI: 0.01, 0.12 mmol/L; P = 0.01, I(2 )= 23%]. Fasting insulin (29 studies, n = 1902; MD: −2.97 pmol/L; 95% CI: −7.05, 1.10 pmol/L; P = 0.15, I(2 )= 21%) and HOMA-IR (13 studies, n = 840; standardized MD: −0.07; 95% CI: −0.26, 0.12; P = 0.49, I(2 )= 38%) were not associated with elevated dairy consumption. HbA1c was negatively associated with elevated dairy product intake in 4 studies (n = 512; MD: −0.09%; 95% CI: −0.09%, −0.03%; P = 0.005, I(2 )= 0%). Most studies had high risk of bias and the quality of evidence was very low or low. In conclusion, evidence suggests that elevated dairy product intake is associated with increased fasting plasma glucose concentrations together with reduced HbA1c in nondiabetic subjects. Hence, the clinical significance of these results remains uncertain. Additional well-designed, long-term studies are required.

This clinical trial investigated the impact of a six-week supplementation with fish oil and single nucleotide polymorphisms (SNPs) in PLA2G4A and PLA2G6 genes on total omega-6 fatty acid (n-6 FA) levels in plasma phospholipids (PL) and plasma C-reactive protein (CRP) levels in 191 subjects. Interaction effects between SNPs and supplementation modulated total n-6 FAs and CRP levels in both men and women. Associations between SNPs and total n-6 FA levels and between SNPs and CRP levels were identified in men, independently of supplementation. Supplementation decreased total n-6 FAs without affecting plasma CRP levels. Changes in CRP levels correlated positively with changes in total n-6 FAs in men (r=0.25 p=0.01), but not in women. In conclusion, total n-6 FA levels in plasma PL and plasma CRP levels are modulated by SNPs within PLA2G4A and PLA2G6 genes alone or in combination with fish oil supplementation.

Evidence suggests that industrial trans fatty acids (iTFA) impair lipid profiles while ruminant trans fatty acids (rTFA) may lower insulin resistance and blood pressure. The objective of this article was to determine if the plasma phospholipid percentage of rTFA is associated with a favorable cardiometabolic profile. We collected fasting blood samples from 200 individuals from Quebec city (QC, Canada) aged from 18 to 55 years old, including 100 obese (BMI ≥ 30 kg m(-2)) and 100 non-obese (BMI30 kg m(-2)) men and women. Fatty acid levels in plasma phospholipids were determined using gas chromatography. After separating the subjects into two groups, according to the median percentage of rTFA in plasma phospholipids, participants in the group with higher percentages of rTFA (0.86 ± 0.24 %) had higher adiponectin levels (p = 0.01) and a lower blood pressure (systolic, p = 0.005; diastolic, p = 0.04). In contrast, concentrations in plasma phospholipids of elaidic acid, a major iTFA, are positively correlated with glycemia in non-obese subjects (p = 0.01) and with both triacylglycerol (TAG) (p = 0.0007) and total cholesterol (TC) (p = 0.009) in obese subjects. These data suggest that rTFA may have beneficial effects on cardiometabolic risk factors conversely to their counterpart iTFA. Dietary sources of TFA should be taken into account in future cardiometabolic studies.

The objective of the present study was to test for associations between changes in fatty acids (FAs) and changes in plasma triglyceride (TG) levels after an n-3 FA supplementation and to test whether SNPs from the FADS gene cluster were associ- ated with plasma FA levels or with specific FA patterns. A total of 210 subjects completed a 2-wk run-in period followed by 6-wk supplementation with 5g/d of fish oil. FA profiles of plasma phospholipids (PPLs) were obtained and 19 SNPs from the FADS gene cluster were genotyped. Principal component analysis was conducted and scores were calculated. There was an increase in EPA, DPA and DHA levels in PPLs as well as a decrease in ALA and all n-6 FA levels after the supplementa- tion. Factor analysis suggested 4 post-n-3 FA supplementation patterns. Changes in AA, ALA, DGLA, as well as changes in total n-3 and omega-6 FAs in absolute quantities of FAs were all associated with a change in TG levels whereas the cor- relation remained significant only for AA and DGLA when FAs were expressed as percentage of total FAs. Several SNPs from the FADS gene cluster were associated with post-supplementation FA levels. These results suggest that FAs alone or regrouped in factors could play a role in modulating plasma TG levels after fish oil supplementation. SNPs from the FADS gene cluster interact with both FAs and/or factors to modulate TG levels.

Background Numbers of single nucleotide polymorphisms (SNPs) associated with fatty acid desaturase activities have been previously identified within the FADS1-FADS2 gene cluster, which encodes delta-5 (D5D) and delta-6 (D6D) desaturases, respectively. Objective We aimed at further characterizing the genetic variability associated with D5D and D6D activities on a genome-wide scale. Methods We conducted a genome-wide association study of D5D and D6D activities in a cohort of 141 individuals from the greater Quebec City metropolitan area using the Illumina HumanOmni5-Quad BeadChip. Estimates of D5D and D6D activities were computed using product-to-precursor fatty acid ratios, arachidonic acid (AA)/dihomo-gamma-linolenic acid (DGLA) for D5D, and DGLA/linoleic acid (LA) for D6D. Levels of fatty acids were measured by gas chromatography in plasma phospholipids. Results We identified 24 previously reported SNPs associated with fatty acid levels and desaturase activities as significantly associated with D5D activity within the FADS1-FADS2 gene cluster (lead SNP rs174566/A>G). Furthermore, we identified 5 novel loci potentially associated with D5D activity at chromosomes 1, 6, 4, 8 and 19. A novel SNP associated with D6D activity and mapped to the ARHGEF10 locus (rs2280885/A>G) was identified, with carriers of the rare allele showing a significant increase in D6D activity and plasma triglyceride levels. After multiple testing correction by permutation, only rs174566 and rs2280885 remained significantly associated to D5D and D6D activity estimates, respectively. Conclusions These results confirm previous genetic associations within the FADS1-FADS2 gene cluster with D5D activity. A novel genetic variation associated with higher D6D activity within the ARHGEF10 gene is potentially altering plasma triglyceride levels.

Dairy intake may reduce the risk of cardiometabolic diseases; yet, the underlying mechanisms remain unclear. Dairy benefits could be attributed to an improvement of low-grade systemic inflammation, a key etiologic factor in the development of cardiometabolic diseases. Macronutrients contained in bovine milk include carbohydrates (lactose), fats and proteins. This chapter focuses on animal and cell studies that reported the effect of dairy macronutrients on inflammation in pertinent tissues, such as adipose tissue, endothelium, liver, intestine, as well as immune cells. Conjugated linoleic acids, casein-derived peptides, leucine, cysteine and glutamine may exert antiinflammatory properties. Yet, studies investigating the effect of specific dairy compounds, such as short-chain, medium-chain, and odd-chain saturated fatty acids, ruminant trans-fatty acids, whey protein hydrolysates, isoleucine, valine or combinations of fatty acids and proteins are scarce. Further investigation is required to characterize the contribution of dairy products on inflammatory response.

SCOPE Metabolomics is increasingly used to identify biomarkers of diet or chronic diseases, such as type 2 diabetes. Yet, metabolite signatures following dairy intake in hyperinsulinemic subjects have not been identified. The objective is to evaluate the effects of a high dairy diet (HD) for 6 weeks (4 servings or more per day), compared with an adequate dairy diet (AD) (2 servings or less per day), on serum metabolite profiles in hyperinsulinemic adults. METHODS AND RESULTS In this crossover trial, subjects are randomized to HD or AD for 6 weeks. Serum metabolites are assessed using GC/MS. Twenty-six subjects completed the study. Levels of pentadecanoic acid, tyrosine and lathosterol are increased in HD, while 1,5-anhydrosorbitol, myo-inositol, 3-aminoisobutyric acid and beta-sitosterol are decreased (p < 0.05). Sorbitol levels are increased after AD, while hexanoic acid, lauric acid, l-kynurenine, methionine, and benzoic acid levels are reduced (p < 0.05). Histidine, caprylic acid, nonanoic acid, decanoic acid, lauric acid, heptadecanoic acid, and benzoic acid levels are increased in HD compared to AD, while malic acid levels are increased in AD compared with HD (p < 0.05). CONCLUSION Higher dairy products intake modifies metabolite profiles in hyperinsulinemic subjects.

Scope To determine if single nucleotide polymorphisms (SNPs) in stearoyl-CoA desaturase (SCD)-1 gene that encodes a key enzyme for fatty acid metabolism are associated with the response of cardiometabolic risk factors to n-3 PUFA supplementation. Methods and results Two hundred and ten subjects completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil (1.9–2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid). Risk factors were measured pre and post n-3 supplementation. Fatty acid composition of plasma phospholipids was analyzed by GC and the desaturase indices SCD16 (16:1n-7/16:0) and SCD18 (18:1n-9/18:0) were calculated. Genotyping of eight SNPs of the SCD1 gene was performed. N-3 PUFA supplementation decreased plasma triglycerides, as well as SCD16 and SCD18 indices, but increased fasting plasma glucose concentrations. SNPs in SCD1-modified cardiometabolic risk factors pre and post n-3 PUFA supplementation: triglyceride (rs508384, p = 0.0086), IL6 (rs3071, p = 0.0485), C-reactive protein (rs3829160, p = 0.0489), and SCD18 indices (rs2234970, p = 0.0337). A significant interaction effect between the SNP and n-3 PUFA supplementation was also observed for fasting plasma glucose levels (rs508384, p = 0.0262). Conclusion These results suggest that cardiometabolic risk factors are modulated by genetic variations in the SCD1 gene alone or in combination with n-3 PUFA supplementation.

The consumption of omega-3 (n-3) fatty acids (FA), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been linked to reduced cardiovascular disease (CVD) risk. The objective of this study was to examine the relation between n-3 FA in plasma phospholipid (PL) levels and CVD risk factors. n-3 FA levels in plasma PL were determined using gas chromatography in 100 obese (body mass index (BMI), ≥30 kg·m−2) and 100 nonobese selected individuals from the Quebec City metropolitan area. The CVD risk factors analysed were BMI, blood pressure, plasma lipids levels, and fasting plasma glucose. Significantly higher levels of alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) were observed in obese subjects, whereas significantly higher levels of DHA were observed in nonobese subjects. For CVD risk factors, ALA levels were positively correlated with plasma triglyceride concentrations and negatively associated with diastolic blood pressure. None of the CVD risk factors studied was linked to EPA levels. In addition, DPA was negatively related to high-density lipoprotein cholesterol (HDL-C) and positively correlated with the total cholesterol/HDL-C ratio. DHA levels were negatively correlated with BMI, waist circumference, and plasma triglyceride levels, whereas a positive association was observed with HDL-C levels. Total n-3 FA percentages were negatively correlated with BMI. In conclusion, higher DHA percentages in plasma PL are associated with a more favourable CVD risk profile, whereas higher DPA percentages in plasma PL are associated with a more deteriorated CVD risk profile.

Background: Marine omega-3 (n-3) polyunsaturated fatty acids (PUFA) reduce plasma triglyceride (TG) levels. Genetic factors such as single nucleotide polymorphisms (SNPs) could be responsible for the variability of the plasma TG response to n-3 PUFA supplementation. Previous studies have demonstrated that n-3 PUFA supplementation using fish oil modified the expression levels of three genes involved in the TG synthesis pathway (GPAM, AGPAT3 and AGPAT4) in peripheral blood mononuclear cells. Methods: A total of 210 subjects consumed 5 g/day of a fish oil supplement for 6 weeks. Plasma lipids were measured before and after the supplementation period. Three SNPs in GPAM, 13 SNPs in AGPAT3 and 35 SNPs in AGPAT4 were genotyped. Results: In an ANOVA for repeated measures adjusted for age, sex and BMI, genotype effects on plasma TG levels were observed for rs1838452 in AGPAT3 as well as for rs746731 and rs2293286 in AGPAT4. Genotype × supplementation interaction effects on plasma TG levels were observed for rs2792751 and rs17129561 in GPAM as well as for rs3798943 and rs9458172 in AGPAT4 (p < 0.05). Conclusion: These results suggest that SNPs in genes involved in the TG synthesis pathway may influence plasma TG levels after n-3 PUFA 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.

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.

Aim: To investigate gene expression changes in peripheral blood mononuclear cells (PBMCs) following an n-3 polyunsaturated fatty acid (PUFA) and n-3 PUFA plus fish gelatin (+FG) supplementation. Methods: A transcriptome comparison of 8-week supplementation with n-3 PUFA and n-3 PUFA+FG was carried out in PBMCs of 16 obese insulin-resistant subjects. Results: Erythrocyte n-3 PUFA concentration increased and plasma triglycerides decreased significantly without altering inflammatory parameters after both supplementations. n-3 PUFA supplementation changed the expression of 805 genes, whereas n-3 PUFA+FG supplementation altered the expression of 184 genes. Three genes were commonly changed: fatty acid desaturase 1, free fatty acid receptor 3, and ectodysplasin. Pathway analyses indicate changes in gene expression via the nuclear receptor peroxisome proliferator-activated receptor α pathway after both supplementations. Further, the extent of modifications in the expression of genes implicated in the inflammatory pathways – the oxidative stress response mediated by nuclear factor (erythroid-derived 2)-like 2, nuclear transcription factor ĸB, oxidative stress, and hypoxia-inducible factor signaling – was different after each supplementation. Conclusion: Although n-3 PUFA and n-3 PUFA+FG supplementations have a distinct impact on gene expression levels, the consequences on biochemical parameters and metabolic pathways were comparable after both supplementations.

The proportion of elderly is growing worldwide. This trend is in parallel to an increase in diseases, such as cardiovascular disease (CVD). Plant sterols and stanols (PS) consumption is known to decrease low-density lipoprotein-cholesterol (LDL-C) levels by 5-15%, and thus lower CVD risk. Yet, the effect of PS on LDL-C levels differs between individuals. Furthermore, PS have recently been investigated for the prevention of other age-related diseases. The objective of this review is to examine the benefits of PS on CVD as well as ageing-associated diseases. PS have the ability to significantly lower LDL-C; yet, the large inter-individual variability in the lowering of LDL-C may be due to subject characteristics, food matrix of PS, dose of PS, dietary background, frequency of intake of PS, the additive effect of other foods or drugs, as well as genetic factors. Further, PS may also have other potential beneficial effects including anti-atherogenic, anti-inflammatory, antioxidant and anti-cancer activities. Overall, dietary intervention strategies, such as incorporating PS into a healthy diet, should be recommended and implemented in older adult populations in order to prevent ageing-associated diseases and hence promote healthy ageing.

Cardiovascular disease (CVD) is responsible for significant morbidity and mortality. Dietary guidelines that aim to manage fat intake reduce CVD, but an important interindividual variability in plasma lipid responsiveness is observed in individuals following these diets. This interdividual variability in response to diets may be attributable to several single nucleotide polymorphisms (SNPs) in genes encoding key proteins involved in lipoprotein metabolism. In this article, we discuss the effect of different diets, classified by type of dietary fats, on plasma lipid levels in relationship to various polymorphisms in key genes that may affect lipid and lipoprotein metabolism. In summary, various polymorphisms may predispose an individual to be more or less responsive to a specific dietary intervention; however, future studies need to be conducted to confirm the effect of these various SNPs. In conclusion, this article reinforces the importance of taking account genetic variability into account in order to p...

Omega-3 fatty acids (FAs) may accelerate plasma triglyceride (TG) clearance by altering lipoprotein lipase (LPL) activity. Yet, the ability of n-3 FAs to increase LPL activity is dependent on transcription factors such as peroxisome proliferator-activated receptor alpha (PPARalpha). The objective was to examine the effects of n-3 FAs on LPL activity considering the occurrence of PPARalpha L162V polymorphism. First, 14 pairs of men either L162 homozygotes or carriers of the V162 allele were supplemented with n-3 FAs. Second, transient transfections in HepG2 cells, for the L162- and V162-PPARalpha variants with the peroxisome proliferator-response element from the human LPL gene, were transactivated with n-3 FAs. In vivo results demonstrate that the LPL activity increased non-significantly by 14.4% in L162 homozygotes compared with 6.6% in carriers of the PPARalpha-V162 allele, after n-3 FA supplementation. Additionally, the L162 homozygotes tended towards an inverse correlation between LPL activities and plasma TG levels. Conversely, carriers of the V162 allele showed no such relationship. In vitro data demonstrates that transcription rates of LPL tended to be higher for the L162-PPARalpha than V162-PPARalpha after n-3 FAs activation. Overall, these results indicate that n-3 FA supplementation increases the transcription rate of LPL to a greater extent in L162-PPARalpha than V162-PPARalpha.

Plant sterols (PS) consumed as a snack may not have the same cholesterol-lowering potential as when consumed with a meal due to poor solubilization. It was hypothesized that the consumption of a single dose, low-fat yogurt rich in PS (1.6 g/d) with a meal over an afternoon snack will lead to favourable changes in plasma lipids, plasma PS concentrations, and cholesterol synthesis without negatively affecting alpha-tocopherol or carotenoids levels.Twenty-six hyperlipidemic males and females completed the randomized trial of three phases (control, single PS dose consumed with a meal, or single PS dose as an afternoon snack) while consuming controlled, low-fat diets. Plasma lipids, cholesterol synthesis rates, plasma PS and serum fat-soluble antioxidants were measured at baseline and after 4 weeks.Endpoint total cholesterol (TC) levels after the PS snack phase were decreased (p = 0.04) (5.30 +/- 0.2 mmol/L) compared to the control phase (5.53 +/- 0.2 mmol/L). However, endpoints for TC (5.37 +/- 0.2 mmol/L) for PS dose with a meal were comparable to control phase. Low-density lipoprotein-cholesterol tended to be different (p = 0.06) at the end of the intervention phases (3.51 +/- 0.1, 3.43 +/- 0.1, and 3.33 +/- 0.1 mmol/L; control, meal and snack, respectively). Cholesterol fractional synthesis rates were higher (p = 0.007) by 25.8% and 19.5% at the end of the snack and meal phases, respectively, compared with the control phase. Plasma campesterol and beta-sitosterol concentrations, adjusted for TC, were higher (p0.01) in the snack phase (2.30 +/- 0.3 and 0.54 +/- 0.1 micromol/mmol, respectively) and in the meal phase (2.00 +/- 0.3 and 0.51 +/- 0.1 micromol/mmol, respectively) when compared to the control phase (1.81 +/- 0.3 and 0.40 +/- 0.1 micromol/mmol, respectively). No changes in alpha-tocopherol or carotenoids levels were detected after adjusting for TC, for all phases.These results indicate that a single dose of PS in low-fat yogurt, provided as a snack, lowers cholesterol levels but does not alter fat-soluble vitamin or carotenoid concentrations in hyperlipidemic participants.

ATP-binding cassette (ABC) transporters function in the homeostasis of lipids. Dysfunction of ABC transporters is frequently associated with disease. This review examines links between polymorphisms of ABC G5 (ABCG5) and G8 (ABCG8) transporter genes to hypercholesterolemia and to gallstone disease risk. Various polymorphisms (A632V, T400K, D19H, M429V, and C54Y) in the ABCG8 and ABCG5 (Q604E) gene have been found to be associated with several facets of cholesterol metabolism, including baseline cholesterol level, cholesterol kinetics, individual responsiveness of plasma cholesterol to dietary and pharmaceutical interventions for hypercholesterolemia, and increased risk of gallstones. Clearly, the ABCG5 and ABCG8 genes play an important role in cholesterol homeostasis. However, more research is needed to establish how specific polymorphisms of these genes confer to higher risk of these diseases.

Cardiovascular disease (CVD) is the leading cause of death in women. Functional food consumption can play an important role in the prevention and treatment of CVD. The purpose of this review is to establish recommendations for the intake of functional food ingredients in a healthy diet, such as soy proteins and isoflavone, omega-3 fatty acids (FAs) from fish oils (FOs) including eicosapentaenoic acid (EPA) and docoshexaenoic acid (DHA) and plant sterols-(PS) enriched foods – for prevention and treatment of CVD in postmenopausal women. First, controversial results exist on CVD risk factors after intake of soy protein and isoflavone that indicates that further clinical studies need to be done to better understand their role in maintaining and improving cholesterol levels. However, since soy contains polyunsaturated fats, replacing some higher fat meat protein sources with soy products may contribute to cardiovascular health. Secondly, FOs, including EPA and DHA, have shown promising effects for lowering triglyceride levels. In addition, emerging research appears to show that omega-3 FAs may have additional health effects with improved arterial health and a reduction in oxidative stress in postmenopausal women. Thirdly, foods and beverages supplemented with PS may reduce cholesterol; therefore, are a worthy addition to interventions aimed at lowering heart disease risk in women. Overall, incorporating functional foods into a healthy diet may be beneficial in helping to reduce lipids levels and thus the risk of CVD.

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.

Cardiovascular disease (CVD) is a major cause of death and disability in many developed countries. The purpose of this literature review is to establish a recommendation for the intake of functional food ingredients in a healthy diet--such as plant sterols (PSs) in low-fat and functional matrices, fatty acid composition and other nutrients of tree nuts and flavonoids in dark chocolate--for the prevention and treatment of CVD. These three specific functional foods are explored in this review, since there is a higher potential for their increased consumption by the population to prevent CVD. First, PS have been added to various nontraditional matrices, such as low-fat products and functional oils, which have shown cholesterol-lowering effects in most clinical trials. Secondly, a growing number of clinical studies indicate that the beneficial effect of tree nuts may not only be due to their fatty acid composition but to other key nutrients, which may provide supplementary health benefits, such as endothelial cell function, as well as decreasing total cholesterol and low-density lipoprotein cholesterol (LDL-C). Lastly, flavonoids in dark chocolate may protect LDL-C particles from undergoing oxidative modification. However, some gaps in our knowledge need to be filled before firm recommendations can be made for habitual dark chocolate consumption. Overall, these functional foods should be considered as an addition to current lipid-lowering recommendations for improving CVD risk.

Background:Fish-oil derived fatty acids (FAs) of the n-3 family including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce inflammation through several underlying mechanisms including altered phospholipids FA composition. The L162V polymorphism of the PPAR-α gene is associated with a deteriorated metabolic profile and with obesity indices in numerous studies. Objective: To study whether the PPAR-α L162V polymorphism and changes in plasma phospholipid FA composition influence plasma C-reactive protein (CRP) levels in healthy adults following the n-3 FA supplementation.Method: 189 subjects were supplemented daily with 3g of n-3 FAs (1.9-2.2g EPA and 1.1g DHA) during six weeks. Changes in CRP levels are defined by Δ CRP and changes in plasma phospholipids n-3 (EPA+DHA) by Δ n-3. Results: In univariate analyses, Δ n-3 was negatively correlated with Δ CRP (r=-0.17 p=0.02). After stratification for sex, correlations were stronger in men (r=-0.24 p=0.02) and no longer significant in women (r=-0....

Phytosterols (PSs) have been recently added to various mediums. Nevertheless, matrices with functional properties, such as medium-chain triglycerides (MCTs), should be precisely examined for supplementary advantages. The objective of this study was to identify the existence of combined biological actions of a functional oil enriched in PSs within MCTs and high-oleic canola (HOC), relative to a control (olive oil), in overweight, hyperlipidemic men using a rigorously controlled dietary intervention. Twenty-three overweight, hyperlipidemic men consumed both types of oil in a randomized, crossover trial for 6 weeks each. Fasted plasma samples were collected on the first and last 2 days of each study period. Body weight decreased -1.22 +/- 0.35 kg (P = .0019) and -1.68 +/- 0.47 kg (P = .0016) after the 6-week study period in the olive oil and functional oil groups, respectively. The end points for total cholesterol and low-density lipoprotein cholesterol (LDL-C) in the functional oil group (P = .0006) were lower than in the olive oil group (P = .0002). Total cholesterol values decreased from comparable baseline to end point of 4.71 +/- 0.16 mmol/L (P < .0001) in the functional oil phase and 5.14 +/- 0.19 mmol/L (P = .0001) in the olive oil phase (P = .0592). In addition, LDL-C demonstrated a similar drop, to an end point of 3.12 +/- 0.16 mmol/L (P < .0001) and 3.54 +/- 0.18 mmol/L (P = .0002), for the functional oil and olive oil groups, respectively, with significant changes (P = .0221). High-density lipoprotein cholesterol levels did not change in either treatment. Triacylglycerol end points decreased in functional oil and olive oil groups (P = .0195 and .0105, respectively) to the same extent from baseline. Results indicate that PSs mixed within an MCT- and HOC-rich matrix lower plasma LDL-C, without significantly changing the high-density lipoprotein cholesterol concentrations, in hyperlipidemic, overweight men, and may therefore decrease the risk of cardiovascular events.

Background Fish oil-derived long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma triglyceride (TG) levels. Genetic factors such as single-nucleotide polymorphisms (SNPs) found in genes involved in metabolic pathways of n-3 PUFA could be responsible for well-recognized heterogeneity in plasma TG response to n-3 PUFA supplementation. Previous studies have shown that genes in the glycerophospholipid metabolism such as phospholipase A2 (PLA2) group II, IV, and VI, demonstrate changes in their expression levels in peripheral blood mononuclear cells (PBMCs) after n-3 PUFA supplementation. Methods A total of 208 subjects consumed 3 g/day of n-3 PUFA for 6 weeks. Plasma lipids were measured before and after the supplementation period. Five SNPs in PLA2G2A, six in PLA2G2C, eight in PLA2G2D, six in PLA2G2F, 22 in PLA2G4A, five in PLA2G6, and nine in PLA2G7 were genotyped. The MIXED Procedure for repeated measures adjusted for age, sex, BMI, and energy intake was used in order to test whether the genotype, supplementation or interaction (genotype by supplementation) were associated with plasma TG levels. Results The n-3 PUFA supplementation had an independent effect on plasma TG levels. Genotype effects on plasma TG levels were observed for rs2301475 in PLA2G2C, rs818571 in PLA2G2F, and rs1569480 in PLA2G4A. Genotype x supplementation interaction effects on plasma TG levels were observed for rs1805018 in PLA2G7 as well as for rs10752979, rs10737277, rs7540602, and rs3820185 in PLA2G4A. Conclusion These results suggest that, SNPs in PLA2 genes may influence plasma TG levels during a supplementation with n-3 PUFA. This trial was registered at clinicaltrials.gov as NCT01343342.

Background Omega-3 (n-3) polyunsaturated fatty acid (PUFA) consumption increases low-density lipoprotein (LDL) cholesterol (C) concentrations and particle size. Studies showed that individuals with large, buoyant LDL particles have decreased risk of cardiovascular diseases. However, a large inter-individual variability is observed in LDL particle size. Genetic factors may explain the variability of LDL-C concentrations and particle size after an n-3 PUFA supplementation. The monoglyceride lipase (MGLL) enzyme, encoded by the MGLL gene, plays an important role in lipid metabolism, especially lipoprotein metabolism. The aim of this study was to investigate if polymorphisms (SNPs) of the MGLL gene influence the variability of LDL-C and LDL particle size in response to an n-3 PUFA supplementation. Methods 210 subjects completed the study. They consumed 5 g/d of a fish oil supplement (1.9-2.2 g eicosapentaenoic acid and 1.1 g docosaexaenoic acid) during 6 weeks. Plasma lipids were measured before and after the supplementation period and 18 SNPs of the MGLL gene, covering 100% of common genetic variations (minor allele frequency ≥0.05), have been genotyped using TaqMan technology (Life Technologies Inc., Burlington, ON, CA). Results Following the n-3 PUFA supplementation, 55% of subjects increased their LDL-C levels. In a model including the supplementation, genotype and supplementation*genotype effects, gene-diet interaction effects on LDL-C concentrations (rs782440, rs6776142, rs555183, rs6780384, rs6787155 and rs1466571) and LDL particle size (rs9877819 and rs13076593) were observed for the MGLL gene SNPs (p

A large inter-individual variability in the plasma triglyceride (TG) response to fish oil consumption has been observed. The objective was to investigate the gene–diet interaction effects between single-nucleotide polymorphisms (SNPs) within glucokinase (GCK) gene and dietary carbohydrate intakes (CHO) on the plasma TG response to a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a 6-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g EPA and 1.1 g DHA). Thirteen SNPs within GCK gene were genotyped using TAQMAN methodology. A gene–diet interaction effect on the plasma TG response was observed with rs741038 and CHO adjusted for age, sex and BMI (p = 0.008). In order to compare the plasma TG response between genotypes according to CHO, participants were divided according to median CHO. Homozygotes of the minor C allele of rs741038 with high CHO >48.59 % had a greater decrease in their plasma TG concentrations following the intake of fish oil (p

Hypolipidemic fibrates activate the peroxisome proliferator-activated receptor (PPAR)αto modulate lipid oxidation and metabolism. The present study aimed at evaluating how 3 PPARαagonists, namely, fenofibrate, gemfibrozil, and Wy14,643, affect bilirubin synthesis and metabolism. Human umbilical vein epithelial cells (HUVEC) and coronary artery smooth muscle cells (CASMC) were cultured in the absence or presence of the 3 activators, and mRNA, protein, and/or activity levels of the bilirubin synthesizing heme oxygenase- (HO-) 1 and biliverdin reductase (BVR) enzymes were determined. Human hepatocytes (HH) and HepG2 cells sustained similar treatments, except that the expression of the bilirubin conjugating UDP-glucuronosyltransferase (UGT) 1A1 enzyme and multidrug resistance-associated protein (MRP) 2 transporter was analyzed. In HUVECs, gemfibrozil, fenofibrate, and Wy14,643 upregulated HO-1 mRNA expression without affecting BVR. Wy14,643 and fenofibrate also caused HO-1 protein accumulation, while gemfibrozil and fenofibrate favored the secretion of bilirubin in cell media. Similar positive regulations were also observed with the 3 PPARαligands in CASMCs where HO-1 mRNA and protein levels were increased. In HH and HepG2 cells, both UGT1A1 and MRP2 transcripts were also accumulating. These observations indicate that PPARαligands activate bilirubin synthesis in vascular cells and metabolism in liver cells. The clinical implications of these regulatory events are discussed.

Studies have shown a large interindividual variability in plasma TG response to long-chain n-3 PUFA supplementation, which may likely be attributable to genetic variability within the populations studied. The objective is to compare the frequency of SNPs in a genome-wide association study between responders (reduction in plasma TG levels ≥0.01 mM) and nonresponders (increase in plasma TG of ≥0 mM) to supplementation. Genomic DNA from 141 subjects who completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil daily (1.9–2.2 g EPA and 1.1 g DHA daily) were genotyped on Illumina HumanOmni-5-QuadBeadChip. Thirteen loci had frequency differences between responders and nonresponders (P < 1 × 10−5), including SNPs in or near IQCJ-SCHIP1, MYB, NELL1, NXPH1, PHF17, and SLIT2 genes. A genetic risk score (GRS) was constructed by summing the number of risk alleles. This GRS explained 21.53% of the variation in TG response to n-3 PUFA supplementation when adjusted for age, sex, and BMI (P = 0.0002). Using Fish Oil Intervention and Genotype as a replication cohort, the GRS was able to explain 2% of variation in TG response when adjusted. In conclusion, subjects who decrease their plasma TG levels following n-3 PUFA supplementation may have a different genetic profile than individuals who do not respond.

(1) Background: A growing body of literature suggest that polymorphisms (SNPs) from inflammation-related genes could possibly play a role in cytokine production and then interact with dietary n-3 fatty acids (FAs) to modulate inflammation. The aim of the present study was to test whether gene expression of selected inflammatory genes was altered following an n-3 PUFA supplementation and to test for gene–diet interactions modulating plasma inflammatory biomarker levels. (2) Methods: 191 subjects completed a 6-week n-3 FA supplementation with 5 g/day of fish oil. Gene expression of TNF-α and IL6 was assessed in peripheral blood mononuclear cells (PBMCs) using the TaqMan technology. Genotyping of 20 SNPs from the TNF-LTA gene cluster, IL1β, IL6 and CRP genes was performed. (3) Results: There was no significant reduction of plasma IL-6, TNF-α and C-reactive protein (CRP) levels after the 6-week fish oil supplementation. TNF-α and IL6 were slightly overexpressed in PBMCs after the supplementation (fold changes of 1.05 ± 0.38 and 1.18 ± 0.49, respectively (n = 191)), but relative quantification (RQ) within the −0.5 to 2.0 fold are considered as nonbiologically significant. In a MIXED model for repeated measures adjusted for the effects of age, sex and BMI, gene by supplementation interaction effects were observed for rs1143627, rs16944, rs1800797, and rs2069840 on IL6 levels, for rs2229094 on TNF-α levels and for rs1800629 on CRP levels (p < 0.05 for all). (4) Conclusions: This study shows that a 6-week n-3 FA supplementation with 5 g/day of fish oil did not alter gene expression levels of TNF-α and IL6 in PBMCs and did not have an impact on inflammatory biomarker levels. However, gene–diet interactions were observed between SNPs within inflammation-related genes modulating plasma inflammatory biomarker levels.

Background Intakes 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). Methods The 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. Results Low 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 n-3 FA: 2.57 g and 1.99 g, p n-3 FA (men: r = 0.47, p Conclusion Estimated 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.