Revisiting multi-omics-based predictors of the plasma triglyceride response to an omega-3 fatty acid supplementation.

Background: The aim of the present study was to identify the metabolomic signature of responders and non-responders to an omega-3 fatty acid (n-3 FA) supplementation, and to test the ability of a multi-omics classifier combining genomic, lipidomic, and metabolomic features to discriminate plasma triglyceride (TG) response phenotypes. Methods: A total of 208 participants of the Fatty Acid Sensor (FAS). Study took 5 g per day of fish oil, providing 1.9-2.2 g eicosapentaenoic acid (EPA) and 1.1 g docosahexaenoic (DHA) daily over a 6-week period, and were further divided into two subgroups: responders and non-responders, according to the change in plasma TG levels after the supplementation. Changes in plasma levels of 6 short-chain fatty acids (SCFA) and 25 bile acids (BA) during the intervention were compared between subgroups using a linear mixed model, and the impact of SCFAs and BAs on the TG response was tested in a mediation analysis. Genotyping was conducted using the Illumina Human Omni-5 Quad BeadChip. Mass spectrometry was used to quantify plasma TG and cholesterol esters levels, as well as plasma SCFA and BA levels. A classifier was developed and tested within the DIABLO framework, which implements a partial least squares-discriminant analysis to multi-omics analysis. Different classifiers were developed by combining data from genomics, lipidomics, and metabolomics. Results: Plasma levels of none of the SCFAs or BAs measured before and after the n-3 FA supplementation were significantly different between responders and non-responders. SCFAs but not BAs were marginally relevant in the classification of plasma TG responses. A classifier built by adding plasma SCFAs and lipidomic layers to genomic data was able to even the accuracy of 85% shown by the genomic predictor alone. Conclusion: These results inform on the marginal relevance of SCFA and BA plasma levels as surrogate measures of gut microbiome in the assessment of the interindividual variability observed in the plasma TG response to an n-3 FA supplementation. Genomic data still represent the best predictor of plasma TG response, and the inclusion of metabolomic data added little to the ability to discriminate the plasma TG response phenotypes.

Docosahexaenoic acid-rich algae oil supplementation in mothers of preterm infants is associated with a modification in breast milk oxylipins profile.

Oxylipins are derived from enzymatic and non-enzymatic oxidation of n-3 and n-6 long-chain polyunsaturated fatty acids. They are known to be involved in inflammatory processes. The aim of this study was to describe the breast milk oxylipin profile following a docosahexaenoic acid (DHA) supplementation of mothers of preterm infants. We examined the oxylipins profile in breast milk collected at day 14 post-delivery, of 40 mothers who delivered before 29 weeks of gestation and who were supplemented with either DHA-rich algae oil (S-DHA) or a placebo (PL). These mothers were selected from the MOBYDIck cohort (NCT02371460 registered on 25/05/2015 in ClinicalTrials.gov) according to the supplementation received (S-DHA vs. PL) and the DHA content quartiles as measured in breast milk (Low vs. High) to generate four study groups. Milk oxylipins, as ng/mL of milk, were analyzed by LC-MS/MS. Ten oxylipins derived from DHA were higher in the S-DHA-High group than the other three groups (P < 0.001). The 18-HEPE, was also higher in the S-DHA-High group (0.11 ± 0.01) compared to the other groups (P = 0.0001). Compared to the PL-Low group, there was a reduction in pro-inflammatory prostaglandins found in the S-DHA-High group with lower levels of prostaglandins PGF2α (0.21 ± 0.45 in the S-DHA-High group vs. 1.87 ± 0.44 in the PL-Low group, P = 0.03) and of PGE2 (0.33 ± 0.26 in the S-DHA-High group vs. 1.28 ± 0.25 in the PL-Low group, P = 0.04).In sum, the DHA supplementation was linked with a predominance of anti-inflammatory oxylipins in breast milk of mothers who delivered very preterm, like 17(S)-HDHA and 18-HEPE, precursors of D and E resolvins respectively. This was also accompanied with a lower level of pro-inflammatory prostaglandins.

Update of a Genetic Risk Score Predictive of the Plasma Triglyceride Response to an Omega-3 Fatty Acid Supplementation in the FAS Study.

A genetic risk score (GRS) predictive of the plasma triglyceride (TG) response to an omega-3 fatty acid (n-3 FA) supplementation has been previously developed in the Fatty Acid Sensor (FAS) Study. Recently, novel single nucleotide polymorphisms (SNPs) interacting with a fish oil supplementation and associated with plasma lipid levels have been identified in the UK Biobank. The aim of this study was to verify whether the addition of SNPs identified in the UK Biobank to the GRS built in the FAS Study improves its capacity to predict the plasma TG response to an n-3 FA supplementation. SNPs interacting with fish oil supplementation in the modulation of plasma lipid levels in the UK Biobank and associated with plasma TG levels have been genotyped in participants of the FAS Study (n = 141). Participants have been supplemented with 5 g fish oil/day for six weeks. Plasma TG concentrations were measured before and after the supplementation. Based on the initial GRS of 31 SNPs (GRS31), we computed three new GRSs by adding new SNPs identified in the UK Biobank: GRS32 (rs55707100), GRS38 (seven new SNPs specifically associated with plasma TG levels), and GRS46 (all 15 new SNPs associated with plasma lipid levels). The initial GRS31 explained 50.1% of the variance in plasma TG levels during the intervention, whereas GRS32, GRS38, and GRS46 explained 49.1%, 45.9%, and 45%, respectively. A significant impact on the probability of being classified as a responder or a nonresponder was found for each of the GRSs analyzed, but none of them outperformed the predictive capacity of GRS31 in any of the metrics analyzed, i.e., accuracy, area under the response operating curve (AUC-ROC), sensitivity, specificity and McFadden's pseudo R2. The addition of SNPs identified in the UK Biobank to the initial GRS31 did not significantly improve its capacity to predict the plasma TG response to an n-3 FA supplementation. Thus, GRS31 still remains the most precise tool so far by which to discriminate the individual responsiveness to n-3 FAs. Further studies are needed in the field to increase our knowledge of factors underlying the heterogeneity observed in the metabolic response to an n-3 FA supplementation.

Industrial and Ruminant Trans-Fatty Acids-Enriched Diets Differentially Modulate the Microbiome and Fecal Metabolites in C57BL/6 Mice.

Industrially originated trans-fatty acids (I-tFAs), such as elaidic acid (EA), and ruminant trans-fatty acids (R-tFAs), such as trans-palmitoleic acid (TPA), may have opposite effects on metabolic health. The objective was to compare the effects of consuming 2-3% I-tFA or R-tFA on the gut microbiome and fecal metabolite profile in mice after 7 and 28 days. Forty C57BL/6 mice were assigned to one of the four prepared formulations: lecithin nanovesicles, lecithin nanovesicles with EA or TPA, or water. Fecal samples and animals' weights were collected on days 0, 7, and 28. Fecal samples were used to determine gut microbiome profiles by 16S rRNA sequencing and metabolite concentrations by GC/MS. At 28 days, TPA intake decreased the abundance of Staphylococcus sp55 but increased Staphylococcus sp119. EA intake also increased the abundance of Staphylococcus sp119 but decreased Ruminococcaceae UCG-014, Lachnospiraceae, and Clostridium sensu stricto 1 at 28 days. Fecal short-chain fatty acids were increased after TPA while decreased after EA after 7 and 28 days. This study shows that TPA and EA modify the abundance of specific microbial taxa and fecal metabolite profiles in distinct ways.

C57bl/6 Mice Show Equivalent Taste Preferences toward Ruminant and Industrial Trans Fatty Acids.

Two distinct types of trans fatty acids (TFA) are found in the diet. Industrial TFA such as elaidic acid (EA) have deleterious effects on metabolic risk factors, and oppositely ruminant TFA including trans-palmitoleic acid (TPA) may have beneficial effects. The objective is to evaluate the taste preference between EA, TPA, lecithin or water. In this study, 24 female C57BL/6 mice were microchipped and placed in two separate IntelliCages®. Nano encapsulated TFA or lecithin were added to drinking water in different corners of the cage with normal diet. The study was carried out over 5 weeks, during which mice were exposed to water only (weeks 1 and 3), TFA or lecithin (week 2), and EA or TPA (weeks 4 and 5). Mice weights, corner visits, nose pokes (NP), and lick number were measured each week. The results demonstrated that mice consume more TFA, either EA or TPA, compared with lecithin. In addition, the mice licked more EA compared with TPA in one cage; conversely, in the other cage they licked more TPA compared with EA. However, when TFA positions were swapped, mice had equal licks for EA and TPA. In sum, mice preferred TFA, in equal matter compared with controls; therefore, the results demonstrate the potential for TFA-type substitution in diet.

Docosahexaenoic acid-rich algae oil supplementation on breast milk fatty acid profile of mothers who delivered prematurely: a randomized clinical trial.

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 < 0.0001), n-6 docosapentaenoic acid (DPA) (0.275 ± 0.14% vs 0.04 ± 0.04%; P < 0.0001) and eicosapentaenoic acid (0.08 ± 0.08% vs 0.07 ± 0.07%; P < 0.0001) while decreasing n-3 DPA (0.16 ± 0.05% vs 0.17 ± 0.06%; P < 0.05). Supplementation changed the ratio of DHA to arachidonic acid (1.76 ± 1.55% vs 0.60 ± 0.31%; P < 0.0001) and n-6 to n-3 FA (0.21 ± 0.06% vs 0.17 ± 0.04%; P < 0.0001). DHA-rich algae supplementation successfully increased the DHA content of breast milk but also included secondary changes that are closely involved with inflammation and may contribute to changing clinical outcomes.

Clinical Practice Guidelines Using GRADE and AGREE II for the Impact of Genetic Variants on Plasma Lipid/Lipoprotein/Apolipoprotein Responsiveness to Omega-3 Fatty Acids.

BACKGROUND: A recent systematic review, which used the GRADE methodology, concluded that there is strong evidence for two gene-diet associations related to omega-3 and plasma triglyceride (TG) responses. Systematic reviews can be used to inform the development of clinical practice guidelines (CPGs). OBJECTIVE: To provide guidance for clinical practice related to genetic testing for evaluating responsiveness to dietary/supplemental omega-3s and their impact on plasma lipids/lipoproteins/apolipoproteins. DESIGN: Using the results of the abovementioned systematic review, the first CPGs in nutrigenetics were developed using the established GRADE methodology and AGREE II approach. RESULTS: Three clinical practice recommendations were developed. Most gene-diet associations identified in the literature lack adequate scientific and clinical validity to warrant consideration for implementing in a practice setting. However, two gene-diet associations with strong evidence (GRADE quality: moderate and high) can be considered for implementation into clinical practice in certain cases: male APOE-E4 carriers (rs429358, rs7412) and TG changes in response to the omega-3 fatty acids eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) as well as a 31-SNP nutrigenetic risk score and TG changes in response to EPA+DHA among adults with overweight/obesity. Ethical and regulatory implications must be considered when providing APOE nutrigenetic tests given the well-established link between APOE genetic variation and Alzheimer's Disease. CONCLUSION: Most of the evidence in this area is not ready for implementation into clinical practice primarily due to low scientific validity (low quality of evidence). However, the first CPGs in nutrigenetics have been developed for two nutrigenetic associations with strong scientific validity, related to dietary/supplemental omega-3 and TG responses.

Residual Solvents in Nanomedicine and Lipid-Based Drug Delivery Systems: a Case Study to Better Understand Processes.

PURPOSE: 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. METHODS: 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. RESULTS: The complete removal of residual solvent requires processes which go beyond usual preparation methods. CONCLUSIONS: 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.

Drinkable lecithin nanovesicles to study the biological effects of individual hydrophobic macronutrients and food preferences.

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.

Prevention of Potential Adverse Metabolic Effects of a Supplementation with Omega-3 Fatty Acids Using a Genetic Score Approach.

INTRODUCTION: The consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) has been reported to have beneficial health effects, notably, by reducing plasma triglyceride levels. Nonetheless, a concomitant decrease in insulin sensitivity has also been observed, but is highly variable among subjects. Herein, we aimed to determine the importance of the genetic background in the interindividual variability of the insulin sensitivity response following an n-3 PUFA supplementation. METHODS: A total of 210 participants completed a 6-week n-3 PUFA supplementation with 5 g/day of fish oil (providing 1.9-2.2 g of eicosapentaenoic acid + 1.1 g of docosahexaenoic acid). Insulin resistance was estimated by the homeostatic model assessment (HOMA-IR), and participants were further classified as high-risk or low-risk depending on their HOMA-IR change following the n-3 PUFA supplementation, as compared to pre-supplementation values. Genome-wide genotyping data were obtained for 138 participants using HumanOmni-5-Quad BeadChips containing 4,301,331 single nucleotide polymorphisms. A genome-wide association analysis (GWAS) was carried out between high-risk and low-risk participants. The population study was split into training (60%) and testing (40%) datasets to assess the predictive accuracy of a genetic risk score (GRS) constructed by summing the number of risk alleles. RESULTS: Following the n-3 PUFA supplementation, 32 participants had increased HOMA-IR as compared to initial values and were classified as high risk (23.2%), whereas remaining subjects were classified as low risk (n = 106, 76.8%). A total of 8 loci had frequency differences between high-risk and low-risk participants at a suggestive GWAS association threshold (p value <1 × 10-5). After applying 10-fold cross validation, the GRS showed a significant association with the risk of increased HOMA-IR in the testing dataset (OR = 3.16 [95% CI, 1.85-7.14]), with a predictive accuracy of 0.85, and explained 40% of variation in HOMA-IR change. CONCLUSIONS: These results suggest that the genetic background has a relevant role in the interindividual variability observed in the insulin sensitivity response following an n-3 PUFA supplementation. Subjects being at risk of insulin sensitivity lowering following an n-3 PUFA supplementation may be identified using genetic-based precision nutrition approaches.

Increased Dairy Product Intake Modifies Plasma Glucose Concentrations and Glycated Hemoglobin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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, I2 = 23%]. Fasting insulin (29 studies, n = 1902; MD: -2.97 pmol/L; 95% CI: -7.05, 1.10 pmol/L; P = 0.15, I2 = 21%) and HOMA-IR (13 studies, n = 840; standardized MD: -0.07; 95% CI: -0.26, 0.12; P = 0.49, I2 = 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, I2 = 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.

Fine mapping of genome-wide association study signals to identify genetic markers of the plasma triglyceride response to an omega-3 fatty acid supplementation.

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.

F2-isoprostanes and fatty acids profile in early pregnancy complicated by pre-existing diabetes.

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.

Polymorphisms in FFAR4 (GPR120) Gene Modulate Insulin Levels and Sensitivity after Fish Oil Supplementation.

The objective was to test whether FFAR4 single nucleotide polymorphisms (SNPs) are associated with glycemic control-related traits in humans following fish oil supplementation. A total of 210 participants were given 3 g/day of omega-3 (n-3) fatty acids (FA) (1.9-2.2 g of eicosapentaenoic acid (EPA) and 1.1 g of docosahexaenoic acid (DHA)) during six weeks. Biochemical parameters were taken before and after the supplementation. Using the HapMap database and the tagger procedure in Haploview, 12 tagging SNPs in FFAR4 were selected and then genotyped using TaqMan technology. Transcript expression levels were measured for 30 participants in peripheral mononuclear blood cells. DNA methylation levels were measured for 35 participants in leukocytes. In silico analyses were also performed. Four gene-diet interactions on fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) index values were found. rs17108973 explained a significant proportion of the variance of insulin levels (3.0%) and HOMA-IR (2.03%) index values. Splice site prediction was different depending on the allele for rs11187527. rs17108973 and rs17484310 had different affinity for transcription factors depending on the allele. n-3 FAs effectively improve insulin-related traits for major allele homozygotes of four FFAR4 SNPs as opposed to carriers of the minor alleles.

Epigenetic changes in blood leukocytes following an omega-3 fatty acid supplementation.

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.

Alterations of fatty acid profiles in gestational diabetes and influence of the diet.

Gestational diabetes mellitus (GDM) is a pregnancy-induced complication with increased prevalence, especially in overweight women. Fatty acid (FA) composition in tissues can reflect dietary fat intake, especially essential FA intake. Moreover, it has been shown that FA profiles in blood lipid fractions are altered in diabetic patients. Consequently, women with GDM may also have a distinctive FA profile. The objective of this review is compare FA profiles in different blood lipid fractions and the influence of dietary fat intake in women with GDM or normoglycemic pregnancies. Results show that women with GDM have more saturated and less polyunsaturated FA (PUFA) in their red blood cell (RBC) membranes than normoglycemic pregnant women. Moreover, some studies reported that women with GDM have a greater energy intake from total fat and saturated FA, along with a lower energy intake from PUFA, when compared to normoglycemic pregnancies. Clinical trials showed that omega-3 PUFA levels in RBC membranes of GDM women can be restored by a dietary intervention. Further research is required to determine whether FA profiles are altered prior to the diagnosis of GDM and can be prevented by diet.

Nutrigenomic point of view on effects and mechanisms of action of ruminant trans fatty acids on insulin resistance and type 2 diabetes.

Evidence from observational studies suggests beneficial effects of ruminant trans fatty acids (rTFA) on insulin resistance (IR) and type 2 diabetes (T2D). However, beneficial effects of rTFA are not always observed in cell, animal, and human studies. This narrative review presents potential mechanisms of action of rTFA using nutrigenomics and microRNA results in an integrative model. In addition, the review presents factors, including measures of IR and T2D, dose and duration of studies, as well as health status, ethnicity, and genotypes of subjects, that may help explain the heterogeneity in response to rTFA supplementation. Future studies should consider these factors, as well as research in nutritional genomics, to better understand the effects of rTFA on IR and T2D.

Plasma Triglyceride Levels May Be Modulated by Gene Expression of IQCJ, NXPH1, PHF17 and MYB in Humans.

A genome-wide association study (GWAS) by our group identified loci associated with the plasma triglyceride (TG) response to ω-3 fatty acid (FA) supplementation in IQCJ, NXPH1, PHF17 and MYB. Our aim is to investigate potential mechanisms underlying the associations between single nucleotide polymorphisms (SNPs) in the four genes and TG levels following ω-3 FA supplementation. 208 subjects received 3 g/day of ω-3 FA (1.9-2.2 g of EPA and 1.1 g of docosahexaenoic acid (DHA)) for six weeks. Plasma TG were measured before and after the intervention. 67 SNPs were selected to increase the density of markers near GWAS hits. Genome-wide expression and methylation analyses were conducted on respectively 30 and 35 participants' blood sample together with in silico analyses. Two SNPs of IQCJ showed different affinities to splice sites depending on alleles. Expression levels were influenced by genotype for one SNP in NXPH1 and one in MYB. Associations between 12 tagged SNPs of IQCJ, 26 of NXPH1, seven of PHF17 and four of MYB and gene-specific CpG site methylation levels were found. The response of plasma TG to ω-3 FA supplementation may be modulated by the effect of DNA methylation on expression levels of genes revealed by GWAS.

Novel Genetic Loci Associated with the Plasma Triglyceride Response to an Omega-3 Fatty Acid Supplementation.

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.

Novel functional foods for optimal oxidative status in healthy ageing.

An antioxidant-rich diet has been shown to reduce the incidence of diet-induced metabolic diseases, such as obesity, diabetes and cardiovascular conditions, and contributes to healthy ageing. Yet, clinical trials investigating common dietary antioxidants, such as vitamins, have often failed to find a significant lowering effect on markers of oxidative stress. This review examines the latest clinical evidence on whether three novel potential antioxidant foods-fish omega-3 fatty acids, red wine and dairy products-can affect the oxidative status of healthy individuals. Clinical studies have reported heterogeneous results regarding the effect of fish oil, red wine and dairy products on oxidative stress. However, numerous studies have suggested that omega-3, red wine and dairy products may lower lipid peroxidation, a known trigger of cardiovascular disease, without affecting the oxidative status of healthy individuals. Overall, this review suggests that consumption of 1-2g/day of omega-3, a moderate red wine intake (200-400ml/day) or 2-3 portions/day of dairy products within a healthy diet exert beneficial effects on oxidative markers. Further investigation to ascertain these effects should focus on the antioxidant effects of long-term omega-3 supplementation, and of intake of dealcoholized red wine or higher dairy product consumption.