title: High-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
abstract: Non-alcoholic fatty liver disease (NAFLD) is emerging as a common medical problem. Nonalcoholic steatohepatitis (NASH) is the critical turning point at which NAFLD progresses to more advanced stages such as hepatic fibrosis, cirrhosis and even hepatocellular carcinoma. However, the study of the pathogenic or therapeutic factors involved in NASH has been hampered by the absence of a suitable experimental model. The aim of the present work was to establish a high-fat emulsion-induced rat model of NASH. Male Sprague-Dawley rats were fed a high-fat emulsion via gavage for 6 weeks. Animals were examined for weight gain, serum and hepatic biochemistry, insulin sensitivity, hepatic malondialdehyde (MDA), superoxide dismutase (SOD) and tissue morphology, as well as cytochrome P-450 2E1 (CYP2E1) and peroxisome proliferator-activated receptor alpha (PPARalpha) expression in the liver. The results showed that rats treated with high-fat emulsion became obese, demonstrated abnormal aminotransferase activity, hyperlipoidemia, hyperinsulinemia, hyperglycemia and insulin resistance. The model rats exhibited an increased concentration of serum TNF-alpha, total cholesterol (TC), triglyceride (TG), MDA and reduced SOD levels in the liver. Immunoblot analysis showed that the expression of CYP2E1 was increased, whereas PPARalpha was reduced in the NASH model rat liver. Moreover, morphological evaluation revealed that hepatic steatosis, inflammation and mitochondrial lesions were also reproduced in this model. In conclusion, a practical and repeatable new rat model of steatohepatitis was established by feeding with high-fat emulsion via gavage. This model provides a valuable research tool and reproduces many of the clinical indices of human NASH.
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Heifei, 230032 Anhui Province, China. zouyuhong318@yahoo.com.cn
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zou
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Lu
authors.forename: Jianqing
authors.initials: J
authors.lastname: Wang
authors.forename: Jinfang
authors.initials: J
authors.lastname: Ge
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D019392:Cytochrome P-450 CYP2E1 / Q000032:analysis; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004655:Emulsions; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size; D047493:PPAR alpha / Q000032:analysis; D051381:Rats / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015430:Weight Gain
chemical_list: D004041:Dietary Fats; D004655:Emulsions; D047493:PPAR alpha; D014409:Tumor Necrosis Factor-alpha; D019392:Cytochrome P-450 CYP2E1