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Mailhot G.,University of Montreal | Rabasa-Lhoret R.,University of Montreal | Moreau A.,University of Montreal | Berthiaume Y.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | Levy E.,University of Montreal
PLoS ONE | Year: 2010

Background: Abnormal fatty acid composition (FA) in plasma and tissue lipids frequently occurs in homozygous and even in heterozygous carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The mechanism(s) underlying these abnormalities remained, however, poorly understood despite the potentially CFTR contributing role. Methodology/Principal Findings: The aim of the present study was to investigate the impact of CFTR depletion on FA uptake, composition and metabolism using the intestinal Caco-2/15 cell line. shRNA-mediated cftr gene silencing induced qualitative and quantitative modifications in FA composition in differentiated enterocytes as determined by gas-liquid chromatography. With the cftr gene disruption, there was a 1,5 fold increase in the total FA amount, largely attributable to monounsaturated and saturated FA compared to controls. The activity of delta-7 desaturase, estimated by the 16:1(n-7)/ 16:0, was significantly higher in knockdown cells and consistent with the striking elevation of the n-7 FA family. When incubated with [14C]-oleic acid, CFTR-depleted cells were capable of quick incorporation and export to the medium concomitantly with the high protein expression of L-FABP known to promote intracellular FA trafficking. Accordingly, lipoprotein vehicles (CM, VLDL, LDL and HDL), isolated from CFTR knockdown cells, exhibited higher levels of radiolabeled FA. Moreover, in the presence of [14C]-acetate, knockdown cells exhibited enhanced secretion of newly synthesized phospholipids, triglycerides, cholesteryl esters and free FA, thereby suggesting a stimulation of the lipogenic pathway. Conformably, gene expression of SREBP-1c, a key lipogenic transcription factor, was increased while protein expression of the phosphorylated and inactive form of acetylCoA carboxylase was reduced, confirming lipogenesis induction. Finally, CFTR-depleted cells exhibited lower gene expression of transcription factors (PPARα, LXRα, LXRβ and RXRα). Conclusions/Significance: Collectively, our results indicate that CFTR depletion may disrupt FA homeostasis in intestinal cells through alterations in FA uptake and transport combined with stimulation of lipogenesis that occurs by an LXR/RXRindependent mechanism. These findings exclude a contributing role of CFTR in CF-associated fat malabsorption. © 2010 Mailhot et al. Source

Ama V.,University of Yaounde I | Kengne A.P.,University of Cape Town | Nansseu N.J.R.,University of Yaounde I | Nouthe B.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | And 2 more authors.
Diabetic Medicine | Year: 2012

Aims To determine the prevalence and effects of sickle cell trait on metabolic control in a Cameroonian diabetic population in a tertiary care setup. Methods This was a cross-sectional study involving 73 consecutive outpatients with Type 2 diabetes recruited from the Yaounde National Diabetes and Obesity Centre. Sickle cell trait status was based on haemoglobin electrophoresis. Metabolic control was assessed by plasma glucose and HbA1c, and comparisons made between participants with and without sickle cell trait, with adjustment for confounders through linear regressions models Results The prevalence of sickle cell trait was 19%, without sex difference, and comparable with figures in individuals without diabetes in this setting. Participants with diabetes and sickle cell trait were older than the non-trait participants (66 vs. 58years, P=0.02). Otherwise, clinical and biological profile including indicators of metabolic control were similarly distributed between trait and non-trait participants (all P>0.08). After adjustment for confounders, sickle cell trait was unrelated to fasting glucose (β=0.02; 95% confidence interval -37.68-43.30) and HbA1c (β=-0.03, 95% confidence interval -1.18-0.93), and did not affect the relationship between the two markers of diabetes control (β=-0.03, 95% confidence interval -1.18-0.89). Conclusions Sickle cell trait was as frequent in this subgroup of patients with Type 2 diabetes as in the general population, suggesting no specific association with diabetes. It does not affect the metabolic control of diabetes. However, how this translates into long-term outcome needs to be fully elucidated in this setting, with an increasing population with both sickle cell trait and diabetes mellitus. © 2012 Diabetes UK. Source

Ekali L.G.,University of Yaounde I | Ekali L.G.,Central Technical Group | Johnstone L.K.,Northumbria University | Echouffo-Tcheugui J.B.,Emory University | And 9 more authors.
Diabetes and Metabolism | Year: 2013

Aims: This study assessed the relationship between highly active antiretroviral therapy (HAART) duration and cardiometabolic disorders in HIV-infected Cameroonians. Methods: HIV-infected Cameroonians aged 21 years or above were cross-sectionally recruited at the Yaoundé Central Hospital, a certified HIV care centre, and their anthropometry, body composition (impedancemetry), fasting blood glucose (FBG) and lipid levels, and insulin sensitivity (IS; short insulin tolerance test) were measured. Results: A total of 143 participants with various durations of HAART [treatment-naïve (n= 28), 1-13 months (n= 44), 14-33 months (n= 35) and 34-86 months (n= 36)] were recruited. They were mostly women (72%), and had a mean age of 39.5 (SD: 9.8) years. Half (52%) were using a stavudine-containing regimen. There was a significant trend towards a positive change in body mass index and waist-to-hip ratio with increasing duration of HAART (all P= 0.02). Systolic (P= 0.04) and diastolic (P= 0.03) blood pressure, total cholesterol (P= 0.01), prevalence of hypertension (P= 0.04) and hypercholesterolaemia (P= 0.007) were also significantly increased with HAART duration, whereas triglycerides, FBG and IS were unaffected. Clustering of metabolic disorders increased (P= 0.02 for ≥ 1 component of the metabolic syndrome and P= 0.09 for ≥ 2 components) with HAART duration. Conclusion: HAART duration is associated with obesity, fat distribution, blood pressure and cholesterol levels in HIV-infected Cameroonians, but does not appear to significantly affect glucose metabolism. © 2012. Source

Boudreau V.,Institute Of Recherches Cliniques Of Montreal | Boudreau V.,University of Montreal | Coriati A.,Institute Of Recherches Cliniques Of Montreal | Coriati A.,University of Montreal | And 5 more authors.
Journal of Cystic Fibrosis | Year: 2016

With improved life expectancy of cystic fibrosis (CF) patients, CF-related diabetes (CFRD) has become a major complication. The oral glucose tolerance test (OGTT) is the standard test to detect it. However, the use of OGTT is controversial, in addition to being a burden for patients and the treatment team. Research to find alternative ways of testing is ongoing. While some propose that glycated hemoglobin (HbA1c) may be an effective alternative, our past results suggest otherwise. A new analysis involving the OGTT and HbA1c values of 207 patients, between 2004 and 2015, proposes that the threshold of a lower value of HbA1c of ≥. 5.8%(39.9 mmol/mol) gives a sensitivity of 68.2% and a specificity of 60.5%. With such sensitivity to identify patients in need of an OGTT, 31.8% of CFRD diagnosis would be missed if the suggested HbA1c value of ≥. 5.8% was used as a screening tool to identify patients in need of OGTTs. Considering our results, we believe the HbA1c does not possess the characteristics of a suitable screening test for CFRD. © 2016 European Cystic Fibrosis Society. Source

Coderre L.,Institute Of Recherches Cliniques Of Montreal | Coderre L.,University of Montreal | Fadainia C.,Institute Of Recherches Cliniques Of Montreal | Belson L.,Institute Of Recherches Cliniques Of Montreal | And 11 more authors.
Journal of Cystic Fibrosis | Year: 2012

Background: The median life expectancy of cystic fibrosis (CF) patients has increased dramatically over the last few years and we now observe a subset of patients with a body mass index (BMI) exceeding 25kg/m2. The aim of this study was to characterize these individuals and to identify factors associated with higher BMI. Methods: This is a cross sectional study including 187 adult CF subjects. Percent predicted forced expiratory volume in 1s (%FEV1), blood lipid profiles as well as fasting glucose and insulin levels were evaluated. Subjects also had an oral glucose tolerance test (OGTT) and the area under the curve (AUC) for glucose and insulin was calculated. CF subjects were then stratified according to the following BMI categories: underweight: BMI≤18.5kg/m2; normal weight: 18.5kg/m2 Source

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