title: Susceptibility of Different Mouse Wild Type Strains to Develop Diet-Induced NAFLD/AFLD-Associated Liver Disease.
abstract: Although non-alcoholic and alcoholic fatty liver disease have been intensively studied, concerning pathophysiological mechanisms are still incompletely understood. This may be due to the use of different animal models and resulting model-associated variation. Therefore, this study aimed to compare three frequently used wild type mouse strains in their susceptibility to develop diet-induced features of non-alcoholic/alcoholic fatty liver disease. Fatty liver disease associated clinical, biochemical, and histological features in C57BL/6, CD-1, and 129Sv WT mice were induced by (i) high-fat diet feeding, (ii) ethanol feeding only, and (iii) the combination of high-fat diet and ethanol feeding. Hepatic and subcutaneous adipose lipid profiles were compared in CD-1 and 129Sv mice. Additionally hepatic fatty acid composition was determined in 129Sv mice. In C57BL/6 mice dietary regimens resulted in heterogeneous hepatic responses, ranging from pronounced steatosis and inflammation to a lack of any features of fatty liver disease. Liver-related serum biochemistry showed high deviations within the regimen groups. CD-1 mice did not exhibit significant changes in metabolic and liver markers and developed no significant steatosis or inflammation as a response to dietary regimens. Although 129Sv mice showed no weight gain, this strain achieved most consistent features of fatty liver disease, apparent from concentration alterations of liver-related serum biochemistry as well as moderate steatosis and inflammation as a result of all dietary regimens. Furthermore, the hepatic lipid profile as well as the fatty acid composition of 129Sv mice were considerably altered, upon feeding the different dietary regimens. Accordingly, diet-induced non-alcoholic/alcoholic fatty liver disease is most consistently promoted in 129Sv mice compared to C57BL/6 and CD-1 mice. As a conclusion, this study demonstrates the importance of genetic background of used mouse strains for modeling diet-induced non-alcoholic/alcoholic fatty liver disease.
authors.affiliation: BioPersMed/Biobank Graz, Medical University of Graz, Graz, Austria.
authors.forename: Vera H I
authors.initials: VH
authors.lastname: Fengler
authors.affiliation: BioPersMed/Biobank Graz, Medical University of Graz, Graz, Austria.
authors.forename: Tanja
authors.initials: T
authors.lastname: Macheiner
authors.affiliation: Department of Pharmacy, Pharmaceutical Biology, Saarland University, Saarbrücken, Germany.
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Kessler
authors.affiliation: Department of Pharmacy, Pharmaceutical Biology, Saarland University, Saarbrücken, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Czepukojc
authors.affiliation: Department of Pharmacy, Pharmaceutical Biotechnology, Saarland University, Saarbrücken, Germany.|Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology (HZI), Saarbrücken, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Gemperlein
authors.affiliation: Department of Pharmacy, Pharmaceutical Biotechnology, Saarland University, Saarbrücken, Germany.|Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology (HZI), Saarbrücken, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.affiliation: Department of Pharmacy, Pharmaceutical Biology, Saarland University, Saarbrücken, Germany.
authors.forename: Alexandra K
authors.initials: AK
authors.lastname: Kiemer
authors.affiliation: Institute for Biomedicine and Health Sciences, Joanneum Research, Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Magnes
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Haybaeck
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Carolin
authors.initials: C
authors.lastname: Lackner
authors.affiliation: BioPersMed/Biobank Graz, Medical University of Graz, Graz, Austria.
authors.forename: Karine
authors.initials: K
authors.lastname: Sargsyan
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D000431:Ethanol / Q000008:administration & dosage*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013045:Species Specificity; D050151:Subcutaneous Fat / Q000378:metabolism* / Q000473:pathology; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D000431:Ethanol; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase