Differential response of two models of genetically modified mice fed with high fat and cholesterol diets: relationship to the study of non-alcoholic steatohepatitis
- 166 Downloads
Research on the molecular basis of the hepatic alterations associated to obesity is dependent on the availability of suitable animal models. Apolipoprotein E deficient mice (ApoE−/−) and LDL-receptor deficient mice (LDLr−/−) develop steatosis and steatohepatitis when given pro-atherogenic diets. However, previous data suggest that these two models are not completely interchangeable, and that their metabolic phenotype may partially differ in response to nutrient stimuli. The present study further investigates this question, by comparing changes in hepatic inflammation, lipoprotein metabolism, and their related gene expressions. LDLr−/− mice were more susceptible to the development of obesity and hepatic steatosis, while the ApoE−/− model increased the amount of macrophages and inflammatory nodules in the liver. These changes were accompanied by a differential expression of selected members of the MAPK family and PPARs in the liver.
KeywordsInflammation Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Steatosis
This work was supported by grants PI05/1606 and PI08/1381 from the Instituto de Salud Carlos III, Madrid, Spain. Anna Rull is the recipient of a fellowship from the Generalitat de Catalunya (FI-G 0503).
Conflict of interest statement
The authors have declared no conflict of interest.
- 6.Begriche K, Igoudjil A, Pessayre D, Fromenty B (2006) Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. Mitochondrion 6:1–28Google Scholar
- 14.Lohmannn C, Schäfer N, von Lukowicz T, Sokrates Stein MA, Borén J, Rütti S, Wahli W, Donath MY, Lüscher TF, Matter CM (2009) Atherosclerotic mice exhibit systemic inflammation in periadventitial and visceral adipose tissue, liver, and pancreatic islets. Atherosclerosis 207:360–367CrossRefGoogle Scholar
- 22.Hasty AH, Shimano H, Osuga J, Namatame I, Takahashi A, Yahagi N, Perrey S, Iizuka Y, Tamura Y, Amemiya-Kudo M, Yoshikawa T, Okazaki H, Ohashi K, Harada K, Matsuzaka T, Sone H, Gotoda T, Nagai R, Ishibashi S, Yamada N (2001) Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor. J Biol Chem 276:37402–37408CrossRefPubMedGoogle Scholar