Personne : Guénard, Frédéric
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Université Laval. Institut sur la nutrition et les aliments fonctionnels
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- PublicationAccès libreAcute effects of single doses of bonito fish peptides and vitamin D on whole blood gene expression levels : a randomized controlled trial(MDPI Center, 2019-04-20) Guénard, Frédéric; Marette, André; Gagnon, Claudia; Vohl, Marie-Claude; Jacques, HélèneFish contains high quality proteins and essential nutrients including 25-hydroxyvitamin D (25(OH)D). Fish peptide consumption can lower cardiovascular disease (CVD) risk factors, and studies have shown an association between 25(OH)D deficiency, CVD and CVD risk factors, such as diabetes. This study investigated acute effects of a single dose of cholecalciferol (VitD3), bonito fish peptide hydrolysate (BPH), or a combination of both on CVD risk factors and whole blood gene expression levels. A randomized, crossover, placebo controlled trial was conducted in 22 adults. They ingested, in random order and at 7-day intervals, 1000 IU of VitD3, 3 g of BPH, a combination of both, or a placebo. A 180 min oral glucose tolerance test was performed. Differences in whole-genome expression levels after versus before each supplementation were computed for 18 subjects. We observed that 16, 1 and 5 transcripts were differentially expressed post- vs. pre-ingestion for VitD3, BPH or VitD3 + BPH treatments, respectively. VitD3-containing treatments affected the expression of the solute carrier family 25 member 20 (SLC25A20) gene involved in fatty acid oxidation, various transcription factors and genes related to glucose metabolism. These results suggest that VitD3 rapidly modulates genes related to CVD risk factors in blood while BPH seems to moderately modulate gene expression levels.
- PublicationAccès libreBariatric surgery induces hypomethylation of genes related to type 2 diabetes and insulin resistance(MedCrave Group, 2017-04-21) Guénard, Frédéric; Toro Martin, Juan de; Marceau, Picard; Deshaies, Yves; Vohl, Marie-Claude; Tchernof, AndréBiliopancreatic diversion with duodenal switch (BPD-DS) is a surgical intervention known to induce substantial weight loss and significant long-lasting metabolic improvements including a decrease in insulin resistance (IR) and resolution of type 2diabetes(T2D). The specific mechanisms by which metabolic improvements occur after BPD-DS are still not fully elucidated and the impact of BPD-DS on gene methylation profiles has not been studied. To gain understanding of epigenetic factors that may predispose to metabolic improvements after weight loss surgery, we characterized the methylation signature of genes associated to T2D and IR after BPD-DS. Most of the genes involved in T2D and IR pathways exhibited significant differences in methylation levels after BPD-DS compared to a pre-surgery control group. The majority of these loci were significantly hypomethylated, suggesting an effect of bariatric surgery on the epigenetic signature of genes encoding proteins involved in glucose homeostasis.
- PublicationAccès libreDifferential methylation of inflammatory and insulinotropic genes after metabolic surgery in women(iMed Pub LLC, 2015-10-03) Guénard, Frédéric; Marceau, Picard; Cianflone, Katherine M.; Deshaies, Yves; Vohl, Marie-Claude; Tchernof, André; Kral, John G.Context: Biliopancreatic diversion with duodenal switch (BPD-DS), a metabolic bariatric operation, induces durable loss of excess weight and reduced cardiometabolic risk. Altered epigenetic marks are mechanistically associated with environment-driven phenotypic variations. Objective: The current study aimed to compare gene methylation levels before and after BPD-DS to identify epigenetic marks potentially linked to metabolic improvements induced by BPD-DS. Design and patients: Metabolic risk factors and gene methylation levels of 20 women studied mean 12 years (range 4-22) after BPD-DS were compared to those of 20 severely obese surgical candidates as controls, matched for pre-surgical age, body mass index and dyslipidemia and hypertension prevalences. Whole-genome blood DNA methylation analysis enabled between-group differential methylation analyses. We calculated correlations between methylation levels of the most differentially methylated CpG sites and plasma glucose and insulin levels and HOMA-IR. Results: Differential methylation analysis identified 15,343 genes demonstrating at least one differentially methylated CpG site (p<1.43x10-7). Diabetic and inflammation/immune functions were among the most overrepresented from the 200 genes exhibiting the largest group differences in methylation levels. CpG sites methylation levels of genes related to insulin action correlated significantly with fasting insulin levels and homeostatic model of insulin resistance (p≤0.002 for all). Conclusion: These findings suggest that differential methylation levels in obese controls versus treated women may partially explain the durable metabolic improvements after BPD-DS.
- PublicationAccès libreGenome-wide association study of the plasma triglyceride response to an n-3 polyunsaturated fatty acid (PUFA) supplementation.(jlr.org, 2014-05-19) Guénard, Frédéric; Rudkowska, Iwona; Barbier, Olivier; Lemieux, Simone; Julien, Pierre; Vohl, Marie-Claude; Calder, Philip C.; Couture, Patrick; Minihane, Anne MarieStudies 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.
- PublicationAccès libreÉvaluation de la contribution de gènes de susceptibilité et de gènes candidats du cancer du sein chez des familles canadiennes françaises à risque élevé(2010) Guénard, Frédéric; Durocher, FrancineLe cancer du sein est une maladie comportant à la fois une composante environnementale et une composante génétique. Dans le cadre de mes études doctorales je me suis intéressé à la composante génétique du cancer du sein. Puisque la distribution de l'héritabilité chez les familles présentant plusieurs cas de cancer du sein suggère la prédominance de facteurs génétiques afin d'expliquer l'agrégation familiale de ce type de cancer, mes études ont porté sur des cas de cancer du sein provenant de familles à risque élevé non porteuses de mutations délétères dans les gènes BRCA1 et BRCA2. Deux volets principaux ont été abordés. Le premier volet, intitulé ± évaluation de la contribution de gènes de susceptibilité au cancer du sein ¿, m'a amené à évaluer la contribution des gènes de susceptibilité à forte penetrance PTENet STK11. Ces gènes sont respectivement responsables des syndromes de Cowden et de Peutz-Jeghers avec lesquels un risque accru de cancer du sein a été associé. Trois autres gènes de susceptibilité au cancer du sein, soit CHEK2, BRIP1 et PALB2, ont également été analysés. Des mutations dans ces gènes confèrent un risque modéré de cancer du sein.Lors du deuxième volet de mon projet, "identification de gènes de susceptibilité au cancer du sein", quatre gènes candidats du cancer du sein ont été analysés. Ces gènes ont été sélectionnés sur la base de leur interaction avec BRCA1. En effet, puisque les protéines encodées par ces gènes interagissent avec BRCA1, elles pourraient réguler ses diverses fonctions. Les gènes AURKA, BAP1, BARD1 et DHX9, encodant respectivement une kinase, une ubiquitine hydrolase, une ubiquitine ligase et une hélicase à ARN, ont été sélectionnés pour leur rôle possible dans la modulation de l'activité de BRCA1 dans la réparation couplée à la transcription. L'étude de ces gènes a permis de mettre en évidence une implication possible d'un variant de BARD1 dans la susceptibilité au cancer du sein. L'étude de ces gènes a permis d'acquérir une meilleure connaissance de la contribution de ceux-ci à la susceptibilité au cancer du sein chez les familles à risque élevé provenant de la population canadienne-française.
- PublicationAccès libreEffect of different concentrations of omega-3 fatty acids on stimulated THP-1 macrophages(Springer-Verlag, 2017-02-21) Guénard, Frédéric; Allam-Ndoul, Bénédicte; Barbier, Olivier; Vohl, Marie-ClaudeBackground: Inflammation plays a central role in chronic diseases occurring in the contemporary society. The health benefits of omega-3 (n-3) fatty acids (FAs), mostly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been reported. However, their mechanisms of action are poorly understood. We explored dose and time effects of EPA, DHA, and a mixture of EPA + DHA on the expression of inflammatory genes in stimulated macrophages. Methods: Lipopolysaccharide was used to stimulate human THP-1 macrophages. Cells were incubated in different conditions in the presence of n-3 FAs and LPS, and mRNA levels of inflammatory genes were measured by real-time PCR. Cytokine levels in culture media were measured. Results: The mixture of EPA + DHA had a more effective inhibitory effect than either DHA or EPA alone, DHA being more potent than EPA. For both EPA and DHA, 75 μM of FAs had a more important anti-inflammatory effect than 10 or 50 μM. For gene expression, EPA had the greater action during the post-incubation (after LPS treatment) condition while DHA and EPA + DHA were more potent during the co-incubation (n-3 FAs and LPS). Cytokine concentrations decreased more markedly in the co-incubation condition. Conclusions: These results suggest that in stimulated macrophages, expression levels of genes involved in inflammation are influenced by the dose, the type of n-3 FAs, and the time of incubation.
- PublicationRestreintDifferential methylation in visceral adipose tissue of obese men discordant for metabolic disturbances(American Physiological Society, 2014-03-15) Guénard, Frédéric; Biron, Simon; Biertho, Laurent; Pérusse, Louis; Lescelleur, Odette; Vohl, Marie-Claude; Deshaies, Yves; Marceau, Simon; Tchernof, AndréObesity is associated with an increased risk of Type 2 diabetes and cardiovascular diseases (CVD). The severely obese population is heterogeneous regarding CVD risk profile. Our objective was to identify metabolic pathways potentially associated with development of metabolic syndrome (MetS) through an analysis of overrepresented pathways from differentially methylated genes between severely obese men with (MetS+) and without (MetS-) the MetS. Genome-wide quantitative DNA methylation analysis in VAT of severely obese men was carried out using the Infinium HumanMethylation450 BeadChip. Differences in methylation levels between MetS+ (n = 7) and MetS- (n = 7) groups were tested. Overrepresented pathways from the list of differentially methylated genes were identified and visualized with the Ingenuity Pathway Analysis system. Differential methylation analysis between MetS+ and MetS- groups identified 8,578 methylation probes (3,258 annotated genes) with significant differences in methylation levels (false discovery rate-corrected DiffScore ≥ |13| ∼ P ≤ 0.05). Pathway analysis from differentially methylated genes identified 41 overrepresented (P ≤ 0.05) pathways. The most overrepresented pathways were related to structural components of the cell membrane, inflammation and immunity and cell cycle regulation. This study provides potential targets associated with adipose tissue dysfunction and development of the MetS.
- PublicationAccès libreA study of the differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on gene expression profiles of stimulated Thp-1 macrophages(MDPI, 2017-01-23) Guénard, Frédéric; Allam-Ndoul, Bénédicte; Barbier, Olivier; Vohl, Marie-ClaudeBackground: An appropriate intake of omega-3 (n-3) fatty acids (FAs) such as eicosapentaenoic and docosahexaenoic acid (EPA/DHA) from marine sources is known to have anti-inflammatory effects. However, molecular mechanisms underlying their beneficial effects on health are not fully understood. The aim of the present study was to characterize gene expression profiles of THP-1 macrophages, incubated in either EPA or DHA and stimulated with lipopolysaccharide (LPS), a pro-inflammatory agent. Methods: THP-1 macrophages were incubated into 10, 50 and 75 µM of EPA or DHA for 24 h, and 100 nM of LPS was added to the culture media for 18 h. Total mRNA was extracted and gene expression examined by microarray analysis using Illumina Human HT-12 expression beadchips (Illumina). Results: Pathway analysis revealed that EPA and DHA regulate genes involved in cell cycle regulation, apoptosis, immune response and inflammation, oxidative stress and cancer pathways in a differential and dose-dependent manner. Conclusions: EPA and DHA appear to exert differential effects on gene expression in THP-1 macrophages. Specific effects of n-3 FAs on gene expression levels are also dose-dependent.
- PublicationAccès libreBody mass index is associated with epigenetic age acceleration in the visceral adipose tissue of subjects with severe obesity(Springer, 2019-12-02) Guénard, Frédéric; Toro Martin, Juan de; Hould, Frédéric-Simon; Vohl, Marie-Claude; Lebel, Stéfane; Tchernof, André; Julien, François; Marceau, SimonBackground There is solid evidence that obesity induces the acceleration of liver epigenetic aging. However, unlike easily accessible blood or subcutaneous adipose tissue, little is known about the impact of obesity on epigenetic aging of metabolically active visceral adipose tissue (VAT). Herein, we aimed to test whether obesity accelerates VAT epigenetic aging in subjects with severe obesity. Results A significant and positive correlation between chronological age and epigenetic age, estimated with a reduced version of the Horvath’s epigenetic clock, was found in both blood (r = 0.78, p = 9.4 × 10−12) and VAT (r = 0.80, p = 1.1 × 10−12). Epigenetic age acceleration, defined as the residual resulting from regressing epigenetic age on chronological age, was significantly correlated with body mass index (BMI) in VAT (r = 0.29, p = 0.037). Multivariate linear regression analysis showed that, after adjusting for chronological age, sex and metabolic syndrome status, BMI remained significantly associated with epigenetic age acceleration in VAT (beta = 0.15, p = 0.035), equivalent to 2.3 years for each 10 BMI units. Binomial logistic regression showed that BMI-adjusted epigenetic age acceleration in VAT was significantly associated with a higher loss of excess body weight following biliopancreatic diversion with duodenal switch surgery (odds ratio = 1.21; 95% CI = 1.04–1.48; p = 0.03). Conclusions Epigenetic age acceleration increases with BMI in VAT, but not in blood, as previously reported in liver. These results suggest that obesity is associated with epigenetic age acceleration of metabolically active tissues. Further studies that deepen the physiological relevance of VAT epigenetic aging will help to better understand the onset of metabolic syndrome and weight loss dynamics following bariatric surgery.
- PublicationAccès libreCharacterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants(Nature Publishing Group, 2015-02-28) Allum, Fiona; Guénard, Frédéric; Shao, Xiaojian; Vohl, Marie-Claude; Lessard, Julie.; Simon, Marie-Michelle; Tchernof, André; Busche, Stephan; Caron, Maxime; Lambourn, John; Tandre, Karolina; Hedman, Asa K.; Kwan, Tony; Ge, Bing; Rönnblom, Lars; McCarthy, Mark I.; Deloukas, Panos; Richmond, Todd; Burgess, Daniel; Spector, T. D. (Timothy David); Marceau, Simon; Lathrop, Mark; Pastinen, Tomi; Grundberg, ElinMost genome-wide methylation studies (EWAS) of multifactorial disease traits use targetedarrays or enrichment methodologies preferentially covering CpG-dense regions, tocharacterize sufficiently large samples. To overcome this limitation, we present here a newcustomizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), forsequencing functional methylomes, while simultaneously providing genetic variationinformation. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adiposetissue (AT) samples and public databases to design AT-specific panels. We establish itsefficiency for high-density interrogation of methylome variability by systematic comparisonswith other approaches and demonstrate its applicability by identifying novel methylationvariation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol,including atCD36. Our more comprehensive AT panel assesses tissue methylation andgenotypes in parallel atB4 andB3 M sites, respectively. Our study demonstrates thatMCC-Seq provides comparable accuracy to alternative approaches but enables more efficientcataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.