Étude de variations génétiques et épigénétiques de gènes candidats des complications métaboliques de l'obésité

L’obésité est de nos jours un problème croissant à travers le monde. La morbidité qui y est associée est surtout reliée au développement des différentes composantes du syndrome métabolique (SMet), une constellation de facteurs de risque regroupant l’hypertension, la dyslipidémie (concentration faible de cholestérol des lipoprotéines à haute densité (C-HDL) et élevée de triglycérides (TG)), l’hyperglycémie et l’obésité. Cependant, certains sujets obèses demeurent métaboliquement sains. Les facteurs génétiques joueraient donc un rôle important dans le développement de l’obésité et de ses complications. Les facteurs épigénétiques semblent également y avoir des effets. L’analyse de tissu adipeux viscéral (TAV) a donc été réalisée pour mener à la découverte de plusieurs gènes différentiellement exprimés et méthylés entre les obèses atteints et non atteints par le SMet. Les deux gènes candidats NMT1 et DGKZ font partie de ce groupe et leurs associations avec les composantes du SMet ont été testées. Leurs niveaux de méthylation et d’expression génique ont aussi été analysés.Obesity is now a major problem worldwide. Its associated morbidity is mostly related to the components of metabolic syndrome (MetS), a constellation of risk factors including hypertension, dyslipidemia (low HDL-C concentration and high concentration of TG), hyperglycemia and obesity. However, some obese subjects remain metabolically healthy. Genetic has thus been established as playing a major role in the development of obesity and its complications. Epigenetic factors may also be involved. The analysis of visceral adipose tissue (VAT) was thus done and led to the discovery of several differentially expressed and methylated genes between groups of obese affected and unaffected with MetS. The two candidate genes NMT1 and DGKZ were part of these and their associations with components of MetS were tested, as well as their methylation and expression levels

Effect of linking arm hydrophilic/hydrophobic nature, length and end-group on the conformation and the RGD accessibility of surface-immobilized fibronectin

In order to stimulate the cellular response to implant materials, extracellular matrix (ECM) proteins, such as collagen and fibronectin (FN), are immobilized on the implant surface. Amongst all ECM proteins used for biomimetic materials for medical applications, FN is one of the most investigated proteins thanks to its ability to promote cell adhesion and its contribution to important physiological processes. However, its conformation and hence its bioactivity strongly depend on the hydrophilic/hydrophobic nature of the surface as well as on immobilization strategies. This work investigates the effect of these two parameters, as well as the effect of the crosslinker length. FN was grafted onto silicon wafers using eights different linking arms presenting different lengths, hydrophilic/hydrophobic characters and binding sites. The protein was linked through either its amino groups (lysine amino acids) or sulfhydryl functionalities (cysteine amino acids). The grafting of each crosslinker and subsequent FN conjugation onto the surfaces was evidenced by X-ray photoelectron spectroscopy, while the surface hydrophilicity was determined by contact angle measurements. Moreover, atomic force microscopy images revealed that the conformation of surface conjugated FN only depends on the hydrophilicity of the linking arm. The FN conformation was also probed by enzyme-linked immunosorbent assays (ELISA). ELISA data demonstrated that all of the three investigated parameters linking arm parameter (length, hydrophobic/hydrophilic character, and terminal end-group) somewhat influence the RGD accessibility

The rare allele of DGKZ SNP rs10838599 is associated with variability in HDL-cholesterol levels among severely obese patients

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

Impact of NMT1 gene polymorphisms on features of the metabolic syndrome among severely obese patients

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

Genetic evidence supports the development of SLC26A9 targeting therapies for the treatment of lung disease

Over 400 variants in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) are CF-causing. CFTR modulators target variants to improve lung function, but marked variability in response exists and current therapies do not address all CF-causing variants highlighting unmet needs. Alternative epithelial ion channel/transporters such as SLC26A9 could compensate for CFTR dysfunction, providing therapeutic targets that may benefit all individuals with CF. We investigate the relationship between rs7512462, a marker of SLC26A9 activity, and lung function pre- and post-treatment with CFTR modulators in Canadian and US CF cohorts, in the general population, and in those with chronic obstructive pulmonary disease (COPD). Rs7512462 CC genotype is associated with greater lung function in CF individuals with minimal function variants (for which there are currently no approved therapies; p = 0.008); and for gating (p = 0.033) and p.Phe508del/ p.Phe508del (p = 0.006) genotypes upon treatment with CFTR modulators. In parallel, human nasal epithelia with CC and p.Phe508del/p.Phe508del after Ussing chamber analysis of a combination of approved and experimental modulator treatments show greater CFTR function (p = 0.0022). Beyond CF, rs7512462 is associated with peak expiratory flow in a meta-analysis of the UK Biobank and Spirometa Consortium (p = 2.74 × 10−44) and provides p = 0.0891 in an analysis of COPD case-control status in the UK Biobank defined by spirometry. These findings support SLC26A9 as a therapeutic target to improve lung function for all people with CF and in individuals with other obstructive lung diseases

Factors Associated with Eating in the Absence of Hunger among Children and Adolescents: A Systematic Review

Eating in the absence of hunger (EAH) has been extensively studied over the past two decades and has been associated with excess body weight and the development of obesity. However, determinants of EAH remain uncertain. This systematic review aims to identify individual, familial, and environmental factors associated with EAH among children and adolescents. We included studies with a measure of EAH in participants aged 3&ndash;17 years old and including &ge;1 factor associated with EAH. Our search identified 1494 articles. Of these, we included 81 studies: 53 cross-sectional, 19 longitudinal and nine intervention studies. In childhood (&le;12 years old), EAH increases with age, it is greater in boys compared to girls, and it is positively associated with adiposity. Moreover, EAH development seems to be influenced by genetics. In adolescence, the number of studies is limited; yet, studies show that EAH slightly increases or remains stable with age, is not clearly different between sexes, and findings for overweight or obesity are less consistent across studies in adolescence. For familial factors, parental restrictive feeding practices are positively associated with EAH during childhood, mostly for girls. Studies assessing environmental factors are lacking and robust longitudinal studies spanning from early childhood to adolescence are needed

Des outils multimédias en ligne pour apprendre des concepts enmathématiques

SAMI-Persévérance est un dispositif d’aide en ligne qui offre, entre autres, des outils d’aide en mathématiques au niveau postsecondaire. Les étudiants peuvent accéder aux outils d’aide par les moyens suivants : par mots-clés, par carte conceptuelle ou par l’outil de dépistage des difficultés en mathématiques. Les données recueillies dans le dispositif révèlent que 4 773 choix d’outils d’aide ont été faits (par l’outil de dépistage dans 72 % des cas), 2 873 énoncés de difficultés ont été cochés, et deux questionnaires sur la dyscalculie ont présenté un résultat positif. Ces données laissent supposer que les étudiants ont apprécié ces outils qui leur ont permis de connaître leurs faiblesses et de mieux comprendre les notions de base en mathématiques.SAMI-Persévérance is an online device that offers help in postsecondary mathematics. Students can access help through the following tools: a keyword search, a concept map, or the math difficulties screening tool. Data collected from the device revealed that 4,773 tool selections were made (72% of the cases were proposed by the screening tool), 2,873 statements of difficulties were checked, and 2 dyscalculia questionnaires showed a positive result. These data suggest that students enjoyed these tools, which allowed them to identify their weaknesses and to understand basic concepts in mathematics

L’alimentation en pleine conscience pour le traitement du trouble d’accès hyperphagique

Cet article discute du recours à l’alimentation en pleine conscience comme approche thérapeutique du trouble d’accès hyperphagique. Caractérisé par la consommation de grandes quantités de nourriture dans un court laps de temps, ce trouble des conduites alimentaires, le plus prévalent d’ailleurs, s’accompagne d’un sentiment de perte de contrôle sur la prise alimentaire et d’une détresse importante. Cette approche donne des résultats positifs en diminuant la fréquence des accès hyperphagiques (AH) et la quantité d’aliments consommés lors d’un AH. Elle intervient sur les trois principaux déclencheurs d’AH : la restriction alimentaire, la restriction cognitive et les envies de manger émotionnelles. La pratique quotidienne et soutenue de la méditation en pleine conscience est le plus important prédicteur des bienfaits. Elle favorise chez la personne qui la pratique la reconnaissance des signaux de la faim et de la satiété permettant ainsi de mieux réguler les apports énergétiques; elle lève les restrictions alimentaires favorisant la reconnaissance des préférences alimentaires et la satisfaction sensorielle; finalement, elle développe la conscience corporelle et l’aptitude à reconnaître les envies de manger émotionnelles qui permettra de diminuer progressivement l’alimentation émotionnelle. Puisque le champ d’exercices des diététistes-nutritionnistes n’englobe pas la modification du fonctionnement émotionnel du client ou de la cliente, une collaboration interprofessionnelle est grandement souhaitable

Quelles sont les stratégies d'apprentissage que les étudiants universitaires ayant un ou des troubles d'apprentissage ou un déficit d'attention doivent apprendre à utiliser?

Au Québec, la présence d’étudiants ayant un ou des troubles d’apprentissage (TA) ou un trouble du déficit d’attention avec ou sans hyperactivité (TDA/H) est de plus en plus marquée dans nos universités. Afin d’aider ces étudiants à persévérer dans leur cheminement universitaire, nous avons voulu connaître les difficultés particulières qu’ils éprouvent sur le plan des stratégies d’apprentissage afin de pouvoir les soutenir d’une façon plus ciblée. Pendant trois sessions d’études, 205 étudiants ont expérimenté un dispositif d’aide à la persévérance aux études, SAMIPersévérance, afin de cerner les difficultés qu’ils rencontraient. Les traces laissées dans le dispositif ont permis de déterminer les stratégies d’apprentissage les moins utilisées autant par les étudiants ayant un TA et ceux ayant un TDA/H que les étudiants ayant les deux types de troubles. Parmi les stratégies d’apprentissage, ce sont les stratégies de lecture, de production écrite, de gestion de la mémorisation, de gestion du temps et de gestion du stress qui semblent les moins utilisées par ces étudiants. Enfin, les étudiants semblent avoir recours à des stratégies de production orale et de gestion de leurs émotions