Personne : Biron, Simon
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Université Laval. Département de chirurgie
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- PublicationRestreintLINE-1 methylation in visceral adipose tissue of severely obese individuals is associated with metabolic syndrome status and related phenotypes.(Springer Nature, 2012-07-02) Biron, Simon; Biertho, Laurent; Pérusse, Louis; Lescelleur, Odette; Bélisle, Alexandre; Turcot, Valérie; Marceau, Simon; Vohl, Marie-Claude; Deshaies, Yves; Tchernof, AndréBackground: Epigenetic mechanisms may be involved in the regulation of genes found to be differentially expressed in the visceral adipose tissue (VAT) of severely obese subjects with (MetS+) versus without (MetS-) metabolic syndrome (MetS). Long interspersed nuclear element 1 (LINE-1) elements DNA methylation levels (% meth) in blood, a marker of global DNA methylation, have recently been associated with fasting glucose, blood lipids, heart diseases and stroke. Aim: To test whether LINE-1%meth levels in VAT are associated with MetS phenotypes and whether they can predict MetS risk in severely obese individuals. Methods: DNA was extracted from VAT of 34 men (MetS-: n = 14, MetS+: n = 20) and 152 premenopausal women (MetS-: n = 84; MetS+: n = 68) undergoing biliopancreatic diversion for the treatment of obesity. LINE-1%meth levels were assessed by pyrosequencing of sodium bisulfite-treated DNA. Results: The mean LINE-1%meth in VAT was of 75.8% (SD = 3.0%). Multiple linear regression analyses revealed that LINE-1%meth was negatively associated with fasting glucose levels (β = -0.04; P = 0.03), diastolic blood pressure (β = -0.65; P = 0.03) and MetS status (β = -0.04; P = 0.004) after adjustments for the effects of age, sex, waist circumference (except for MetS status) and smoking. While dividing subjects into quartiles based on their LINE-1%meth (Q1 to Q4: lower %meth to higher %meth levels), greater risk were observed in the first (Q1: odds ratio (OR) = 4.37, P = 0.004) and the second (Q2: OR = 4.76, P = 0.002) quartiles compared to Q4 (1.00) when adjusting for age, sex and smoking. Conclusions: These results suggest that lower global DNA methylation, assessed by LINE-1 repetitive elements methylation analysis, would be associated with a greater risk for MetS in the presence of obesity.
- PublicationAccès libreCharacterization of dedifferentiating human mature adipocytes from the 6 visceral and subcutaneous fat compartments : fibroblast-activation protein 7 alpha and Dipeptidyl peptidase 4 as major components of matrix remodeling(Public Library of Science, 2015-03-27) Biron, Simon; Biertho, Laurent; Lescelleur, Odette; Hould, Frédéric-Simon; Marceau, Simon; Marceau, Picard; Moustarah, Fady; Lebel, Stéfane; Pelletier, Mélissa; Lessard, Julie.; Tchernof, AndréMature adipocytes can reverse their phenotype to become fibroblast-like cells. This is achieved by ceiling culture and the resulting cells, called dedifferentiated fat (DFAT) cells, are multipotent. Beyond the potential value of these cells for regenerative medicine, the dedifferentiation process itself raises many questions about cellular plasticity and the pathways implicated in cell behavior. This work has been performed with the objective of obtaining new information on adipocyte dedifferentiation, especially pertaining to new targets that may be involved in cellular fate changes. To do so, omental and subcutaneous mature adipocytes sampled from severely obese subjects have been dedifferentiated by ceiling culture. An experimental design with various time points along the dedifferentiation process has been utilized to better understand this process. Cell size, gene and protein expression as well as cytokine secretion were investigated. Il-6, IL-8, SerpinE1 and VEGF secretion were increased during dedifferentiation, whereas MIF-1 secretion was transiently increased. A marked decrease in expression of mature adipocyte transcripts (PPARγ2, C/EBPα, LPL and Adiponectin) was detected early in the process. In addition, some matrix remodeling transcripts (FAP, DPP4, MMP1 and TGFβ1) were rapidly and strongly up-regulated. FAP and DPP4 proteins were simultaneously induced in dedifferentiating mature adipocytes supporting a potential role for these enzymes in adipose tissue remodeling and cell plasticity.
- PublicationAccès libreTemporal changes in gene expression profile during mature adipocyte dedifferentiation(Hindawi Publishing Corporation, 2017-03-19) Guénard, Frédéric; Biron, Simon; Lapointe, Marc; Vohl, Marie-Claude; Côté, Julie Anne; Lessard, Julie.; Tchernof, AndréObjective. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture. Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures was performed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changes was used to identify overrepresented functions. Results. Four clusters gathered genes with similar expression between day 4 to day 7 but decreasing expression from day 7 to day 12. Most of these genes coded for proteins involved in adipocyte functions (LIPE, PLIN1, DGAT2, PNPLA2, ADIPOQ, CEBPA, LPL, FABP4, SCD, INSR, and LEP). Expression of several genes coding for proteins implicated in cellular proliferation and growth or cell cycle increased significantly from day 7 to day 12 (WNT5A, KITLG, and FGF5). Genes coding for extracellular matrix proteins were differentially expressed between days 0, 4, 7, and 12 (COL1A1, COL1A2, and COL6A3, MMP1, and TGFB1). Conclusion. Dedifferentiation is associated with downregulation of transcripts encoding proteins involved in mature adipocyte functions and upregulation of genes involved in matrix remodeling, cellular development, and cell cycle.
- PublicationRestreintWaist girth does not predict metabolic complications in severely obese men(American Diabetes Association, 2006-05-26) Drapeau, Vicky; Biron, Simon; Mauriege, Pascale; Richard, Denis; Marceau, Picard; Lemieux, Isabelle.; Bergeron, JeanThe epidemic of obesity has received considerable attention because of its increasing prevalence and its deleterious impact on health. In this regard, the metabolic syndrome has been recognized as a prevalent cause of cardiovascular disease, and the National Cholesterol Education Program Adult Treatment Panel III guidelines have proposed clinical tools for the identification of individuals characterized by this syndrome. However, there is considerable metabolic heterogeneity among equally overweight/ obese individuals. While some patients show a relatively “normal” metabolic risk profile despite being obese, others who are moderately overweight can nevertheless be characterized by metabolic complications. Thus, it is not uncommon to find severely obese patients with minimal changes in their metabolic risk profile, suggesting that they may be at lower cardiovascular disease risk than what could be expected from their massive obesity. Therefore, the aim of the present study was to examine the relationships between selected features of the metabolic syndrome and waist circumference as a crude marker of abdominal obesity in moderately and severely obese men.
- PublicationRestreintWaist circumference is useless to assess the prevalence of metabolic abnormalities in severely obese women(Springer, 2007-07-14) Drapeau, Vicky; Biron, Simon; Mauriege, Pascale; Tremblay, Angelo; Richard, Denis; Marceau, Picard; Lemieux, Isabelle.; Bergeron, JeanBackground : The present retrospective study aims to provide additional evidence supporting the fact that waist circumference, in severe obesity, is not a good clinical marker to identify individuals with the metabolic syndrome or an altered metabolic profile. Methods : Relationships between waist circumference and metabolic profile of pre- (n = 165) and postmenopausal (n = 43) severely obese women were compared to associations observed in pre- (n = 52) and postmenopausal (n = 35) moderately obese women. Results : Results showed that abdominal obesity assessed by waist circumference was more highly correlated with fasting glycemia, HDL-cholesterol and the cholesterol/HDL-cholesterol ratio in moderately than in severely obese women, before menopause. After menopause, waist circumference was not a valuable predictor of metabolic abnormalities in both groups. Moreover, when waist circumference was included as a criterion of the metabolic syndrome (as defined by the NCEP ATP III guidelines) in severely obese women, the prevalence of this metabolic condition was over-estimated by 72%. Conclusion : These results emphasize the uselessness of waist circumference to assess the prevalence of the metabolic syndrome or an altered metabolic profile in severely obese women.
- 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 libreBiliopancreatic diversion with duodenal switch in the elderly : long-term results of a matched-control study(Springer, 2015-07-01) Marchand, Geneviève B.; Biron, Simon; Biertho, Laurent; Lebel, Stéfane; Lescelleur, Odette; Nadeau, Mélanie; Marceau, Simon; Hould, Frédéric-Simon; Michaud, Andréanne; Tchernof, AndréBackground : Biliopancreatic diversion with duodenal switch (BPD-DS) is one of the most effective surgical approaches for the treatment of severe obesity. Objective : The objective of this study is to compare perioperative complications and long-term results of open BPD-DS in elderly versus younger patients. Methods : All patients aged 60 years and above who underwent a primary open BPD-DS in our center were selected (n = 105). Patients were matched 1:1 for sex, BMI, the presence of type 2 diabetes (T2DM), and year of surgery with a group of younger patients (aged ≤55 years). Results : The mean age of the patients was 62.3 ± 2.0 vs. 40.4 ± 7.0 years (p ≤ 0.0001). Initial BMI and prevalence of T2DM were similar in both groups, at 50.9 kg/m2 and 57 %, respectively. Mean operative time (178.6 ± 46.7 vs. 162.5 ± 39.9 min, p = 0.01), hospital stay (10.2 ± 8.3 vs. 6.3 ± 1.5 days, p = 0.0001), and blood loss (593 ± 484 vs. 474 ± 241 ml, p = 0.05) were significantly higher in elderly patients. No difference in 30-day mortality rate was observed (0.9 % in each group). There was no significant difference in major complication rate (16.2 vs. 8.6 %, p = 0.09). At a mean follow-up of 7.1 ± 4.1 years, excess weight loss (67.6 ± 19.2 vs. 72.7 ± 20.7 %, p = 0.06) and BMI (32.2 ± 5.7 vs. 30.8 ± 6.6 kg/m2, p = 0.15) were not significantly different. No significant difference was observed between the two groups for the resolution of T2DM (p = 0.53) and obstructive sleep apnea (p = 0.44). Conclusions : Open BPD-DS is associated with similar long-term benefits in elderly and younger patients, in terms of weight loss and resolution or improvement of obesity-related comorbidities. Perioperative complications might be more frequent in the elderly population, but this was not associated with increased mortality.
- PublicationRestreintZFP36 : a promising candidate gene for obesity-related metabolic complications identified by converging genomics(Springer, 2007-03-31) Biron, Simon; Lescelleur, Odette; Vohl, Marie-Claude; Marceau, Simon; Deshaies, Yves; Bouchard, Luigi; Tchernof, AndréBackground : Few genes have been associated with the metabolic syndrome (MS), although its genetic component is well accepted. The aim of this study was to compare the adipose tissue gene expression profiles of obese men with and without the MS and to apply an integrative genomic approach to propose new candidate genes. Methods : Affymetrix HG-U133 plus 2 arrays have been used for expression profiling of omental adipose tissue of non-diabetic obese men with (n=7) and without (n=7) the MS, as defined by the NCEP-ATPIII, that undergo a bariatric operation. Results ; Omentum expresses a total of 23 055 transcripts. Overall, 489 genes were differentially expressed between the two groups. A total of 80 differentially expressed genes were located within a previously identified region of linkage. In this subset of genes, zinc finger protein 36 (ZFP36) gene has been identified as the most promising genetic target for the MS-based mean fold expression differences and on biological plausibility. 2 out of 5 identified ZFP36 gene polymorphisms have been genotyped in a cohort of 698 obese subjects. The minor allele of these polymorphisms was associated with a lower body weight in women (rs251864; P≤0.01) and glucose level in men (c.1564_1565delTT; P<0.05). The haplogenotype was associated with plasma LDL-cholesterol levels in men and women (P≤0.02), and weight in women (P≤0.05). The haplogenotype was also associated with omental adipose tissue ZFP36 mRNA levels (n=83 women; P=0.02), and explained 10.1% of its variance. Conclusion : These results suggest that converging genomics is helpful to prioritize MS-related candidate genes and that ZFP36 is a promising candidate gene for obesity-associated metabolic complications.
- PublicationAccès libreImpact 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, SimonIntroduction: 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.
- PublicationRestreintDPP4 gene DNA methylation in the omentum is associated with its gene expression and plasma lipid profile in severe obesity(The Obesity Society, 2012-09-06) Biron, Simon; Biertho, Laurent; Pérusse, Louis; Lescelleur, Odette; Turcot, Valérie; Faucher, Geneviève; Bélisle, Alexandre; Vohl, Marie-Claude; Marceau, Simon; Deshaies, Yves; Bouchard, Luigi; Tchernof, AndréSeverely obese subjects with the metabolic syndrome (MS) have higher dipeptidyl peptidase‐4 (DPP4) expression in their visceral adipose tissue (VAT) compared to obese individuals without MS. We tested the hypothesis that methylation level of CpG sites in the DPP4 promoter CpG island in VAT was genotype‐dependent and associated with DPP4 mRNA abundance and MS‐related phenotypes. The VAT DNA was extracted in 92 severely obese premenopausal women undergoing biliopancreatic derivation for the treatment of obesity. Women were nondiabetic and none of them used medication to treat MS features. Cytosine methylation rates (%) of 102 CpG sites in the DPP4 CpG island were assessed by pyrosequencing of sodium bisulfite‐treated DNA. Methylation rates were >10% for CpG sites 94–102. Their mean methylation rate (%Meth94–102) was different between genotypes for DPP4 polymorphisms rs13015258 (P = 0.001), rs17848915 (P = 0.0004), and c.1926 G>A (P = 0.001). The %Meth94–102 correlated negatively with DPP4 mRNA abundance (r = −0.25, P < 0.05) and positively with plasma high‐density lipoprotein (HDL) cholesterol concentrations (r = 0.22, P < 0.05), whereas DPP4 mRNA abundance correlated positively with plasma total‐/HDL‐cholesterol ratio (r = 0.25; P < 0.05). In the VAT of nondiabetic severely obese women, genotype‐dependent methylation levels of specific CpG sites in the DPP4 promoter CpG island were associated with DPP4 gene expression and variability in the plasma lipid profile. Higher DPP4 gene expression in VAT and its relationship with the plasma lipid profile may be explained by actually unknown DPP4 biological effect or, to another extent, may also be a marker of VAT inflammation known to be associated with metabolic disturbances.