title: Diet-induced dyslipidemia leads to nonalcoholic fatty liver disease and oxidative stress in guinea pigs.
abstract: Chronic dyslipidemia imposed by a high-fat and high-caloric dietary regime leads to debilitating disorders such as obesity, nonalcoholic fatty liver disease (NAFLD), and insulin resistance. As disease rates surge, so does the need for high validity animal models to effectively study the causal relationship between diet and disease progression. The dyslipidemic guinea pig displays a high similarity with the human lipoprotein profile and may in this aspect be superior to other rodent models. This study investigated the effects of 2 long-term Westernized diets (0.35% cholesterol, 18.5% vegetable oil and either 15% or 20% sucrose) compared with isocaloric standard chow in adult guinea pigs. Biochemical markers confirmed dyslipidemia in agreement with dietary regimens; however, both high-fat groups displayed a decreased tissue fat percentage compared with controls. Macroscopic appearance, histopathologic evaluation, and plasma markers of liver function confirmed NAFLD in high-fat groups, supported by liver redox imbalance and markers suggesting hepatic endothelial dysfunction. Plasma markers indicated endothelial dysfunction in response to a high-fat diet, although atherosclerotic lesions were not evident. Evaluation of glucose tolerance showed no indication of insulin resistance. The 5% increase in sucrose between the 2 high-fat diets did not lead to significant differences between groups. In conclusion, we find the dyslipidemic guinea pig to be a valid model of diet imposed dyslipidemia, particularly with regards to hepatic steatosis and endothelial dysfunction. Furthermore, the absence of obesity supports the present study setup as targeting NAFLD in nonobese individuals.
authors.affiliation: Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Tveden-Nyborg
authors.affiliation: Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Malene M
authors.initials: MM
authors.lastname: Birck
authors.affiliation: Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: David H
authors.initials: DH
authors.lastname: Ipsen
authors.affiliation: Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Thiessen
authors.affiliation: Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Linda de Bie
authors.initials: LB
authors.lastname: Feldmann
authors.affiliation: Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Maiken M
authors.initials: MM
authors.lastname: Lindblad
authors.affiliation: Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Jensen
authors.affiliation: Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark. Electronic address: jopl@sund.ku.dk.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
mesh_terms: D000818:Animals; D001823:Body Composition; D004041:Dietary Fats / Q000009:adverse effects* / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000150:complications*; D005260:Female; D005951:Glucose Tolerance Test; D006168:Guinea Pigs; D008099:Liver / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000209:etiology*; D018384:Oxidative Stress / Q000502:physiology*; D013154:Spleen
chemical_list: D004041:Dietary Fats