title: High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are closely related. Diet plays an important role in the progression of these diseases, but the role of specific dietary components is not completely understood. Therefore, we investigated the role of dietary sucrose and fat/cholesterol on the development of dyslipidemia and NAFLD.
  
  
  METHODS
  Seventy female guinea pigs were block-randomized (based on weight) into five groups and fed a normal chow diet (control: 4 % fat), a very high-sucrose diet (vHS: 4 % fat, 25 % sucrose), a high-fat diet (HF: 20 % fat, 0.35 % cholesterol), a high-fat/high-sucrose diet (HFHS: 20 % fat, 15 % sucrose, 0.35 % cholesterol) or a high-fat/very high-sucrose diet (HFvHS: 20 % fat, 25 % sucrose, 0.35 % cholesterol) for 16 and 25 weeks.
  
  
  RESULTS
  All three high-fat diets induced dyslipidemia with increased concentrations of plasma cholesterol (p < 0.0001), LDL-C (p < 0.0001) and VLDL-C (p < 0.05) compared to control and vHS. Contrary to this, plasma triglycerides were increased in control and vHS compared to high-fat fed animals (p < 0.01), while circulating levels of free fatty acids were even between groups. Histological evaluation of liver sections revealed non-alcoholic steatohepatitis (NASH) with progressive inflammation and bridging fibrosis in high-fat fed animals. Accordingly, hepatic triglycerides (p < 0.05) and cholesterol (p < 0.0001) was increased alongside elevated levels of alanine and aspartate aminotransferase (p < 0.01) compared to control and vHS.
  
  
  CONCLUSIONS
  Collectively, our results suggest that intake of fat and cholesterol, but not sucrose, are the main factors driving the development and progression of dyslipidemia and NAFLD/NASH.
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.
authors: David Højland
authors: DH
authors: Ipsen
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.
authors: Pernille
authors: P
authors: Tveden-Nyborg
authors: Diabetes Pharmacology, Global research, Novo Nordisk, Novo Nordisk Park 1, 2760 Måløv, Denmark.
authors: Bidda
authors: B
authors: Rolin
authors: Diabetes Pharmacology, Global research, Novo Nordisk, Novo Nordisk Park 1, 2760 Måløv, Denmark.
authors: Günaj
authors: G
authors: Rakipovski
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.
authors: Maria
authors: M
authors: Beck
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.
authors: Line Winther
authors: LW
authors: Mortensen
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.
authors: Lasse
authors: L
authors: Færk
authors: National Veterinary Institute, Technical University of Denmark, Bülowsvej 27, 1870 Frederiksberg C, Denmark.
authors: Peter Mikael Helweg
authors: PM
authors: Heegaard
authors: Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, 1353 Copenhagen, Denmark.
authors: Peter
authors: P
authors: Møller
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.
authors: Jens
authors: J
authors: Lykkesfeldt
keywords: Cholesterol; Dyslipidemia; Guinea pigs; High-fat diet; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Sucrose