title: Feeding apolipoprotein E-knockout mice with cholesterol and fat enriched diets may be a model of non-alcoholic steatohepatitis.
abstract: The present study was aimed (1) to investigate the effect of cholesterol and fat enriched diets on the development of steatohepatitis in apolipoprotein E-knockout mice, and (2) to study the chronological relationships between the development of hepatic alterations, hypercholesterolemia and atherosclerotic lesions in this experimental model. The study consisted of two protocols. Protocol 1 was used in 90 mice subdivided in groups of 18. For 10 weeks, each group was given a diet with different fat and cholesterol contents. Protocol 2 was used in 42 mice, subdivided in four groups. Each group was given a diet enriched with cholesterol and palm oil and they were sacrificed at 8, 13, 18 and 24 weeks of age. Results were as following. (1) Mice given high fat/high cholesterol diets developed an impairment of liver histology consisting of fat accumulation, macrophage proliferation, and inflammation. (2) These effects were modulated by the type of fat: olive oil was mainly associated with macrovesicular steatosis and cholesterol plus palm oil with severe steatohepatitis. (3) There was a chronological and quantitative relationship between liver impairment and the formation of atheromatous lesions. We conclude that apolipoprotein E-knockout mice may be a useful model for investigating the mechanisms of diet-induced steatohepatitis.
authors.affiliation: Centre de Recerca Biomèdica, Institut de Recerca en Ciències de la Salut, Hospital Universitari de Sant Joan, 43201-Reus, Catalunya, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Tous
authors.forename: Natàlia
authors.initials: N
authors.lastname: Ferré
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
authors.forename: Francesc
authors.initials: F
authors.lastname: Riu
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006505:Hepatitis; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; D002791:Cholesterol, Dietary
references.citation: Am J Gastroenterol. 1999 Sep;94(9):2467-74
references.pmid: 10484010
references.citation: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3433-7
references.pmid: 10725355
references.citation: Am J Physiol. 1999 Jan;276(1 Pt 2):R136-42
references.pmid: 9887187
references.citation: Arterioscler Thromb Vasc Biol. 1999 Oct;19(10 ):2368-75
references.pmid: 10521366
references.citation: Arterioscler Thromb Vasc Biol. 1997 Jan;17(1):119-26
references.pmid: 9012646
references.citation: Science. 1992 Oct 16;258(5081):468-71
references.pmid: 1411543
references.citation: Hepatology. 1996 Jul;24(1):241-7
references.pmid: 8707269
references.citation: Med Clin North Am. 1996 Sep;80(5):1147-66
references.pmid: 8804378
references.citation: Semin Liver Dis. 2001;21(1):89-104
references.pmid: 11296700
references.citation: Cell. 1992 Oct 16;71(2):343-53
references.pmid: 1423598
references.citation: Proc Natl Acad Sci U S A. 1992 May 15;89(10):4471-5
references.pmid: 1584779
references.citation: Cancer Res. 2001 Jul 1;61(13):5016-23
references.pmid: 11431335
references.citation: J Clin Invest. 1996 Oct 1;98(7):1575-84
references.pmid: 8833906
references.citation: Semin Liver Dis. 2001;21(1):27-41
references.pmid: 11296694
references.citation: J Lipid Res. 1993 Sep;34(9):1555-64
references.pmid: 8228638
references.citation: Atherosclerosis. 1987 Dec;68(3):231-40
references.pmid: 3426656
references.citation: J Clin Invest. 1994 Aug;94(2):877-84
references.pmid: 8040344
references.citation: Hepatology. 2002 Apr;35(4):753-61
references.pmid: 11915020
references.citation: Best Pract Res Clin Gastroenterol. 2002 Oct;16(5):679-90
references.pmid: 12406439
references.citation: Mayo Clin Proc. 1980 Jul;55(7):434-8
references.pmid: 7382552
references.citation: Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G193-9
references.pmid: 11804839
references.citation: Curr Opin Lipidol. 2000 Feb;11(1):25-9
references.pmid: 10750690
references.citation: Genes Dev. 1998 Oct 15;12(20):3182-94
references.pmid: 9784493
references.citation: Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2557-62
references.pmid: 9122234
references.citation: Atherosclerosis. 1994 Nov;111(1):25-37
references.pmid: 7840811
references.citation: Am J Physiol Gastrointest Liver Physiol. 2002 Jan;282(1):G1-5
references.pmid: 11751151
references.citation: Genes Dev. 1998 Oct 15;12(20):3168-81
references.pmid: 9784492
references.citation: J Gastroenterol Hepatol. 1997 May;12(5):398-403
references.pmid: 9195388
references.citation: Arterioscler Thromb Vasc Biol. 2001 Jun;21(6):991-6
references.pmid: 11397709
references.citation: Atherosclerosis. 1998 Mar;137(1):1-11
references.pmid: 9568731
references.citation: J Lipid Res. 1995 Nov;36(11):2320-8
references.pmid: 8656070
references.citation: Gastroenterology. 2001 Apr;120(5):1183-92
references.pmid: 11266382
references.citation: J Biol Chem. 1999 Feb 26;274(9):5692-700
references.pmid: 10026188
references.citation: Prog Biochem Pharmacol. 1986;21:104-34
references.pmid: 3523499
references.citation: Mol Cell Biochem. 2001 Feb;218(1-2):165-9
references.pmid: 11330832
references.citation: Life Sci. 2002 Jan 11;70(8):855-65
references.pmid: 11853223