Emilie Catry1, Audrey M Neyrinck1, Irina Lobysheva2, Barbara D Pachikian1, Matthias Van Hul1,3, Patrice D Cani1,3, Chantal Dessy2, Nathalie M Delzenne4. 1. Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium. 2. Pôle de Pharmacologie et Thérapeutique, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium. 3. Walloon Excellence in Life sciences and Biotechnology (WELBIO), Wavre, Belgium. 4. Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium. nathalie.delzenne@uclouvain.be.
Abstract
SCOPE: Western diets are characterized by low intake of n-3 PUFA compensated by constant amounts of n-6 PUFA. Reduced intake of n-3 PUFA is associated with increased cardiovascular risk, as observed in nonalcoholic fatty liver disease patients. The study aimed to evaluating the impact of dietary n-3 PUFA depletion on endothelial function, an early key event of cardiovascular diseases. METHODS AND RESULTS: C57Bl/6J or apolipoprotein E knock-out (apoE-/- ) were fed control (CT) or n-3 PUFA-depleted diets (DEF) for 12 wks. Mice fed n-3 DEF diet developed a hepatic steatosis, linked to changes in hepatic expression of genes controlled by Sterol Regulatory Element Binding Protein-1 and -2. Vascular function was assessed on second- and third-order mesenteric arteries and n-3 PUFA-depleted apoE-/- mice presented endothelial dysfunction characterized by decreased vasorelaxation in response of acetylcholine. The presence of a nitric oxide synthase (NOS) inhibitor blunted the relaxation in each groups and heme-nitrosylated hemoglobin blood (Hb-NO) level was significantly lower in n-3 PUFA-depleted apoE-/- mice. CONCLUSION: Twelve weeks of n-3 DEF diet promote steatosis and accelerate the process of endothelial dysfunction in apoE-/- mice by a mechanism involving the NOS/NO pathway. We propose n-3 PUFA-depleted apoE-/- mice as a new model to study endothelial dysfunction related to hepatic steatosis independently of obesity.
SCOPE: Western diets are characterized by low intake of n-3 PUFA compensated by constant amounts of n-6 PUFA. Reduced intake of n-3 PUFA is associated with increased cardiovascular risk, as observed in nonalcoholic fatty liver diseasepatients. The study aimed to evaluating the impact of dietary n-3 PUFA depletion on endothelial function, an early key event of cardiovascular diseases. METHODS AND RESULTS: C57Bl/6J or apolipoprotein E knock-out (apoE-/- ) were fed control (CT) or n-3 PUFA-depleted diets (DEF) for 12 wks. Mice fed n-3 DEF diet developed a hepatic steatosis, linked to changes in hepatic expression of genes controlled by Sterol Regulatory Element Binding Protein-1 and -2. Vascular function was assessed on second- and third-order mesenteric arteries and n-3 PUFA-depleted apoE-/- mice presented endothelial dysfunction characterized by decreased vasorelaxation in response of acetylcholine. The presence of a nitric oxide synthase (NOS) inhibitor blunted the relaxation in each groups and heme-nitrosylated hemoglobin blood (Hb-NO) level was significantly lower in n-3 PUFA-depleted apoE-/- mice. CONCLUSION: Twelve weeks of n-3 DEF diet promote steatosis and accelerate the process of endothelial dysfunction in apoE-/- mice by a mechanism involving the NOS/NO pathway. We propose n-3 PUFA-depleted apoE-/- mice as a new model to study endothelial dysfunction related to hepatic steatosis independently of obesity.
Authors: Audrey M Neyrinck; Emilie Catry; Bernard Taminiau; Patrice D Cani; Laure B Bindels; Georges Daube; Chantal Dessy; Nathalie M Delzenne Journal: Sci Rep Date: 2019-10-02 Impact factor: 4.379
Authors: Emilie Catry; Laure B Bindels; Anne Tailleux; Sophie Lestavel; Audrey M Neyrinck; Jean-François Goossens; Irina Lobysheva; Hubert Plovier; Ahmed Essaghir; Jean-Baptiste Demoulin; Caroline Bouzin; Barbara D Pachikian; Patrice D Cani; Bart Staels; Chantal Dessy; Nathalie M Delzenne Journal: Gut Date: 2017-04-04 Impact factor: 23.059