Personne :
Pérusse, Louis

En cours de chargement...
Photo de profil
Adresse électronique
Date de naissance
Projets de recherche
Structures organisationnelles
Nom de famille
Université Laval. Département de kinésiologie
Identifiant Canadiana

Résultats de recherche

Voici les éléments 1 - 10 sur 16
  • Publication
    Differential 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, André
    Obesity 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.
  • Publication
    Accès libre
    Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
    (Nature Publishing Group, 2017-04-26) Justice, Anne E.; Pérusse, Louis; Vohl, Marie-Claude; Cupples, L. Adrienne
    Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
  • Publication
    Relation between a BglII polymorphism in 3 beta-hydroxysteroid dehydrogenase gene and adipose tissue distribution in humans
    (North American Association for the Study of Obesity, 1994-09-01) Bouchard, Claude; Dionne, France T.; Pérusse, Louis; Dériaz, Olivier; Vohl, Marie-Claude; Chagnon, Monique
    The aim of this study was to investigate the association between a restriction fragment length polymorphism (RFLP) at the 3β‐hydroxysteroid dehydrogenase locus and adipose tissue distribution pheno‐types. A total of 132 unrelated individuals from the Quebec Family Study were followed prospectively for an average period of 11.3 years. The Bgl II polymorphism in exon 4 of the 3β‐HSD gene was detected by PCR. Body mass, body fat, and regional fat distribution indicators were adjusted for age and age2 within each gender. Associations were assessed in unrelated adults with ANOVA across three genotypes. No association was found for the indicators of body mass, body fat, and regional distribution of adipose tissue measured in 1992. In women, the changes (difference between data collected in 1992 and at entry) in the sum of six skinfolds (p=0.04), abdominal skinfold (p=0.01), and abdominal skinfold adjusted (p=0.03) for the sum of six skinfolds at entry were related to the Bgl II polymorphism at the 3β‐HSD locus. These relations were not found in men, but they gained less body mass and body fat over the 11.3‐year period. This suggests that sequence variation at the 3β‐HSD locus or in neighboring genes on chromosome 1 may contribute to individual differences in body fat content and adipose tissue distribution in adult women, particularly in abdominal adipose tissue deposition as they grow older and gain body fat.
  • Publication
    Accès libre
    Association between metabolite profiles, metabolic syndrome and obesity status
    (MDPI, 2016-05-27) Allam-Ndoul, Bénédicte; Guénard, Frédéric; Cormier, Hubert; Garneau, Véronique; Pérusse, Louis; Barbier, Olivier; Vohl, Marie-Claude
    Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW) and overweight/obese (Ov/Ob) individuals, with or without metabolic syndrome (MetS). Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1’s (long chain glycerophospholipids) metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C) and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C) among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine) was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3’s (medium chain acylcarnitines) metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.
  • Publication
    Accès libre
    The rare allele of DGKZ SNP rs10838599 is associated with variability in HDL-cholesterol levels among severely obese patients
    (Open Access Text Pvt. Ltd, 2016-05-12) Guénard, Frédéric; Pérusse, Louis; Hould, Frédéric-Simon; Deshaies, Yves; Marceau, Picard; Bégin, Stéphanie; Vohl, Marie-Claude; Lebel, Stéfane; Tchernof, André
    Introduction: Diacylglycerol kinase-zeta, one of the ten isoforms of DGKs expressed in mammals is an important enzyme of lipid metabolism. It catalyzes the interconversion of diacylglycerol and phosphatidic acid, two major second messengers. Its gene DGKZ has been previously identified as being overexpressed and undermethylated in visceral adipose tissue of patients with (MetS+) versus without (MetS-) the metabolic syndrome (MetS). Objective: The aim of this study was to investigate the associations between DGKZ gene polymorphisms (SNPs) and phenotypes related to MetS (BMI, waist girth, CRP, fasting glucose, lipid profile (triglycerides, total-cholesterol, LDL-cholesterol and HDL-cholesterol (HDL-C)), resting systolic and diastolic blood pressures). Methods: The study sample included 1752 severely obese participants who underwent bariatric surgery. Associations between the five selected tSNPs of DGKZ and features of the MetS were tested. The effects of these SNPs on DGKZ methylation and expression levels were tested in subgroups of 32 and 14 obese subjects, respectively. Correlations between methylation and expression levels were also computed. Results: Homozygotes for the rare allele of rs10838599 displayed higher plasma HDL-C concentrations compared to the other genotype groups (p=0.03). For gene methylation, only a trend with the cg05412031 CpG site (p=0.09) was found for the single significantly phenotype-associated SNP. There was no significant correlation between DGKZ methylation at cg05412031 and expression levels. Conclusion: These results suggest that DGKZ SNP rs10838599 modulates plasma HDL-C levels thereby its gene contributes to the inter-individual variability observed in the cardiometabolic risk profile of patients with severe obesity.
  • Publication
    Differential epigenomic and transcriptomic responses in subcutaneous adipose tissue between low and high responders to caloric restriction
    (Oxford University Press, 2009-11-25) Pérusse, Louis; Rabasa-Lhoret, Rémi; Vohl, Marie-Claude; Faraj, May; Bouchard, Luigi; Lavoie, Marie-Ève; Mill, Jonathan
    Background: Caloric restriction is recommended for the treatment of obesity, but it is generally characterized by large interindividual variability in responses. The factors affecting the magnitude of weight loss remain poorly understood. Epigenetic factors (ie, heritable but reversible changes to genomic function that regulate gene expression independently of DNA sequence) may explain some of the interindividual variability seen in weight-loss responses. Objective: The objective was to determine whether epigenetics and gene expression changes may play a role in weight-loss responsiveness. Design: Overweight/obese postmenopausal women were recruited for a standard 6-mo caloric restriction intervention. Abdominal subcutaneous adipose tissue biopsy samples were collected before (n = 14) and after (n = 14) intervention, and the epigenomic and transcriptomic profiles of the high and low responders to dieting, on the basis of changes in percentage body fat, were compared by using microarray analysis. Results: Significant DNA methylation differences at 35 loci were found between the high and low responders before dieting, with 3 regions showing differential methylation after intervention. Some of these regions contained genes known to be involved in weight control and insulin secretion, whereas others were localized in known imprinted genomic regions. Differences in gene expression profiles were observed only after dieting, with 644 genes being differentially expressed between the 2 groups. These included genes likely to be involved in metabolic pathways related to angiogenesis and cerebellar long-term depression. Conclusions: These data show that both DNA methylation and gene expression are responsive to caloric restriction and provide new insights about the molecular pathways involved in body weight loss as well as methylation regulation during adulthood.
  • Publication
    Accès libre
    Impact of NMT1 gene polymorphisms on features of the metabolic syndrome among severely obese patients
    (Openventio Publishers, 2015-11-24) Guénard, Frédéric; Biron, Simon; Biertho, Laurent; Deshaies, Yves; Pérusse, Louis; Lescelleur, Odette; Bégin, Stéphanie; Vohl, Marie-Claude; Tchernof, André; Marceau, Simon
    Introduction: N-myristoyltransferase (NMT) is implicated in myristoylation, required for biological activities of several proteins. Its gene N-myristoyltransferase 1 (NMT1) has been found to be overexpressed and hypermethylated in Visceral Adipose Tissue (VAT) of severely obese individuals with Metabolic Syndrome (MetS+) versus without (MetS-). Objective: The aim of this study was to verify the associations between NMT1 gene polymorphisms Single Nucleotide Polymorphisms (SNPs) and metabolic complications among obese subjects. Methods: Associations between SNPs and determinants of MetS were tested with 1752 obese participants undergoing a bariatric surgery. The effect of selected SNPs on methylation, and correlation with expression levels of NMT1 were verified in subgroups. Results: Rs2239921 was significantly associated with systolic (p=0.03) and diastolic (p<0.0001) blood pressures. Rs2239923 was associated with plasma High Density Lipoprotein-Cholesterol or HDL-Cholesterol (HDL-C) levels (p=0.05), while rs2269746 was associated with Low Density Lipoprotein-Cholesterol or LDL-Cholesterol (LDL-C) (p=0.006) and Total-Cholesterol (Total-C) levels (p=0.004). Rs1005136 (p=0.03), rs8066395 (p=0.03) or rs2157840 (p=0.04) were associated with plasma concentrations of C-Reactive Protein (CRP). Phenotype-associated SNPs were associated with NMT1 methylation levels of six CpG sites. NMT1 methylation levels of one CpG site, cg10755730, correlated with gene expression levels (r=0.57; p=0.04). Conclusion: These results suggest that the presence of NMT1 SNPs is associated with altered plasma lipid levels as well as with increased inflammation markers and blood pressure among severely obese patients.
  • Publication
    Association between olfactory receptor genes, eating behavior traits and adiposity : results from the Quebec Family Study
    (Pergamon Press, 2011-10-25) Drapeau, Vicky; Choquette, Anne.; Bouchard, Claude; Pérusse, Louis; Tremblay, Angelo; Lemieux, Simone; Vohl, Marie-Claude; Bouchard, Luigi
    Obesity is a major health problem that can be influenced by eating behaviors. Evidence suggests that the sensory properties of food influence eating behaviors and lead to overeating and overweight. A previous genome-wide linkage scan for eating behavior traits assessed with the Three-Factor Eating Questionnaire (cognitive dietary restraint, disinhibition and hunger) performed in the Quebec Family Study (QFS) revealed a quantitative trait locus for disinhibition on chromosome 19p13. This region encodes a cluster of seven olfactory receptor (OR) genes, including OR7D4, previously associated with odor perceptions. Direct sequencing of the OR7D4 gene revealed 16 sequence variants. Nine OR7D4 sequence variants with minor allele frequency (MAF) > 1% as well as 100 SNPs spanning the cluster of OR genes on 19p13 were tested for association with age- and sex-adjusted eating behaviors as well as adiposity traits in 890 subjects. One OR7D4 sequence variant (rs2878329 G > A) showed evidence of association with reduced levels of adiposity (p = 0.03), cognitive dietary restraint (p = 0.05) and susceptibility to hunger (p = 0.008). None of the OR7D4 SNPs was associated with disinhibition, but a SNP (rs2240927) in another OR gene (OR7E24) showed evidence of association (p = 0.03). Another SNP in the OR7G3 gene (rs10414255) was also found to be associated with adiposity and eating behaviors. These results are the first to suggest that variations in human olfactory receptor genes can influence eating behaviors and adiposity. The associations reported in the present study should be interpreted with caution considering the number of tests performed and considered as potential new hypotheses about the effects OR polymorphisms on eating behaviors and obesity that need to be further explored in other populations.
  • Publication
    Accès libre
    The challenge of stratifying obesity : attempts in the Quebec family study
    (Frontiers Research Foundation, 2019-10-10) Guénard, Frédéric; Bouchard, Claude; Toro Martin, Juan de; Pérusse, Louis; Tremblay, Angelo; Vohl, Marie-Claude
    Background and aims: Obesity is a major health problem worldwide. Given the heterogeneous obesity phenotype, an optimal obesity stratification would improve clinical management. Since obesity has a strong genetic component, we aimed to develop a polygenic risk score (PRS) to stratify obesity according to the genetic background of the individuals. Methods: A total of 231 single nucleotide polymorphisms (SNP) significantly associated to body mass index (BMI) from 21 genome-wide association studies were genotyped or imputed in 881 subjects from the Quebec Family Study (QFS). The population was randomly split into discovery (80%; n = 704) and validation (20%; n = 177) samples with similar obesity (BMI ≥ 30) prevalence (27.8% and 28.2%, respectively). Family-based associations with obesity were tested for every SNP in the discovery sample and a weighed and continuous PRS231 was constructed. Generalized linear mixed effects models were used to test the association of PRS231 with obesity in the QFS discovery sample and validated in the QFS replication sample. Furthermore, the Fatty Acid Sensor (FAS) Study (n = 141; 27.7% obesity prevalence) was used as an independent sample to replicate the results. Results: The linear trend test demonstrated a significant association of PRS231 with obesity in the QFS discovery sample (ORtrend = 1.19 [95% CI, 1.14-1.24]; P = 2.0x10-16). We also found that the obesity prevalence was significantly greater in the higher PRS231 quintiles compared to the lowest quintile. Significant and consistent results were obtained in the QFS validation sample for both the linear trend test (ORtrend = 1.16 [95% CI, 1.07-1.26]; P = 6.7x10-4), and obesity prevalence across quintiles. These results were partially replicated in the FAS sample (ORtrend = 1.12 [95% CI, 1.02-1.24]; P = 2.2x10-2). PRS231 explained 7.5%, 3.2%, and 1.2% of BMI variance in QFS discovery, QFS validation, and FAS samples, respectively. Conclusions: These results revealed that genetic background in the form of a 231 BMI-associated PRS has a significant impact on obesity, but a limited potential to accurately stratify it. Further studies are encouraged on larger populations.
  • Publication
    Accès libre
    A GWAS follow-up of obesity-related SNPs in SYPL2 reveals sexspecific association with hip circumference
    (John Wiley & Sons Inc., 2016-09-20) Guénard, Frédéric; Biron, Simon; Toro Martin, Juan de; Biertho, Laurent; Pérusse, Louis; Lescelleur, Odette; Vohl, Marie-Claude; Deshaies, Yves; Marceau, Simon; Tchernof, André
    Objective A novel single-nucleotide polymorphism (SNP) associated with morbid obesity was recently identified by exome sequencing. The purpose of this study was to follow up this low-frequency coding SNP located within the SYPL2 locus and associated with body mass index in order to reveal novel associations with obesity-related traits. Methods The body mass index-associated SNP (rs62623713 A>G [chr1:109476817/hg19]) and two tagging SNPs within the SYPL2 locus, rs9661614 T>C (chr1:109479215) and rs485660 G>A (chr1:109480810), were genotyped in the obesity (n = 3,017) and the infogene (n = 676) cohorts, which were further combined, leading to a larger cohort of 3,693 individuals. Association testing was performed by general linear models in the obesity cohort and validated by joint analysis in the combined cohort. Results rs9661614 and rs485660 were significantly associated with hip circumference (HC) in the obesity cohort, with heterozygotes exhibiting a significantly lower HC. These results were validated by joint analysis for rs9661614 (false discovery rate [FDR]-corrected P = 7.5 × 10−4) and, to a lesser extent, for rs485660 (FDR corrected P = 3.9 × 10−2). The association with HC remained significant for rs9661614 when tested independently in women (FDR-corrected P = 1.7 × 10−2), but not for rs485660 (FDR-corrected P = 0.2). Both associations were absent in men. Conclusions This study reveals strong evidence for a novel association between rs9661614 (T>C) and HC in women, which likely reflects a preferential association of SYPL2 to a gynoid profile of fat distribution. The study findings support a clinical significance of SYPL2 worth considering when assessing risk factors associated with obesity.