title: Nutritional depletion in n-3 PUFA in apoE knock-out mice: A new model of endothelial dysfunction associated with fatty liver disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Emilie
authors.initials: E
authors.lastname: Catry
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Neyrinck
authors.affiliation: Pôle de Pharmacologie et Thérapeutique, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Irina
authors.initials: I
authors.lastname: Lobysheva
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Pachikian
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.|Walloon Excellence in Life sciences and Biotechnology (WELBIO), Wavre, Belgium.
authors.forename: Matthias
authors.initials: M
authors.lastname: Van Hul
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.|Walloon Excellence in Life sciences and Biotechnology (WELBIO), Wavre, Belgium.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.affiliation: Pôle de Pharmacologie et Thérapeutique, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Dessy
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium. nathalie.delzenne@uclouvain.be.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000209:etiology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism / Q000493:pharmacokinetics; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000503:physiopathology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D015525:Fatty Acids, Omega-3; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D009569:Nitric Oxide; D000109:Acetylcholine
keywords: Endothelial dysfunction; Liver; Nitric oxide; apoE knock-out mice; n-3 PUFA