title: High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications.
abstract: BACKGROUND
  As a result of the increased consumption of sugar-rich and fatty-products, and the increase in preference for such products, metabolic disorders are becoming more common at a younger age. Fructose is particularly used in prepared foods and carbonated beverages. We investigated the impact of regular consumption of fructose, in combination or not with fatty food, on the onset of metabolic syndrome and type 2 diabetes (T2D). We evaluated the metabolic, oxidative, and functional effects on the liver and blood vessels, both related to diabetes complications.
  
  
  METHODS
  High-fat diet (HFD), high-fructose beverages (HF) or both (HFHF) were compared to rats fed with normal diet (ND) for 8 months to induce T2D and its metabolic, oxidative, and functional complications. Metabolic control was determined by measuring body weight, fasting blood glucose, C-peptide, HOMA2-IR, leptin, and cholesterol; oxidative parameters were studied by lipid peroxidation and total antioxidant capacity in plasma and the use of ROS labelling on tissue. Histological analysis was performed on the liver and endothelial function was performed in main mesenteric artery using organ-baths.
  
  
  RESULTS
  After 2 months, HFHF and HFD increased body weight, leptin, HOMA2-IR associated to steatosis, oxidative stress in plasma and tissues, whereas HF had only a transient increase of leptin and c-peptide. Only HFHF induced fasting hyperglycaemia after 6 months and persistent hyperinsulinaemia and fasting hyperglycaemia with complicated steatosis (inflammation and fibrosis) after 8 months. HFHF and HFD induced endothelial dysfunction at 8 months of diet.
  
  
  CONCLUSIONS
  Six months, high fat and high carbohydrate induced T2D with widespread tissues effects. We demonstrated the role of oxidative stress in pathogenesis as well as in complications (hepatic and vascular), reinforcing interest in the use of antioxidants in the prevention and treatment of metabolic diseases, including T2D.
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France.
authors.forename: Iona
authors.initials: I
authors.lastname: Lozano
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France ; Equipe de Chimie Analytique des Molécules BioActives, IPHC-LC4, UMR 7178, Faculté de Pharmacie, Ilkirch, France.
authors.forename: Remmelt
authors.initials: R
authors.lastname: Van der Werf
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France.
authors.forename: William
authors.initials: W
authors.lastname: Bietiger
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Seyfritz
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Peronet
authors.affiliation: Structure d'Endocrinologie, Diabète, Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg, (HUS), 67000 Strasbourg, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Pinget
authors.affiliation: Structure d'Endocrinologie, Diabète, Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg, (HUS), 67000 Strasbourg, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jeandidier
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Maillard
authors.affiliation: Equipe de Chimie Analytique des Molécules BioActives, IPHC-LC4, UMR 7178, Faculté de Pharmacie, Ilkirch, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Marchioni
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Sigrist
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, 67200 Strasbourg, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dal
keywords: Endothelial dysfunction; Hepatic complications; High-fat high-fructose diet; Metabolic syndrome; Oxidative stress; Type 2 diabetes; Vascular complications