Characterization of High-Fat, Diet-Induced, Non-alcoholic Steatohepatitis with Fibrosis in Rats

• Published in: Digestive diseases and sciences 2010-04, Vol.55 (4), p.931-940
• Main Authors: Xu, Zheng-Jie, Fan, Jian-Gao, Ding, Xiao-Dong, Qiao, Liang, Wang, Guo-Liang
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Biochemistry; Biological and medical sciences; Blood Glucose - metabolism; Body weight; Cholesterol; Cholesterol - metabolism; Diet; Dietary Fats - pharmacology; Disease Models, Animal; Fatty acids; Fatty Acids, Nonesterified - metabolism; Fatty Liver - pathology; Feeding. Feeding behavior; Fibrosis; Fundamental and applied biological sciences. Psychology; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatology; Insulin - metabolism; Insulin resistance; Liver - pathology; Liver Cirrhosis, Experimental - immunology; Liver Cirrhosis, Experimental - pathology; Liver diseases; Liver Function Tests; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Medicine; Medicine & Public Health; Obesity, Abdominal - immunology; Obesity, Abdominal - pathology; Oncology; Original; Original Article; Other diseases. Semiology; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta1 - metabolism; Transforming growth factors; Transplant Surgery; Triglycerides - metabolism; Tumor Necrosis Factor-alpha - metabolism; Type 2 diabetes; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Weight Gain - physiology
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-009-0815-3

An ideal animal model is necessary for a clear understanding of the etiology, pathogenesis, and mechanisms of human non-alcoholic steatohepatitis (NASH) and for facilitating the design of effective therapy for this condition. We aimed to establish a rat model of NASH with fibrosis by using a high-fat diet (HFD). Male Sprague-Dawley (SD) rats were fed a HFD consisting of 88 g normal diet, 10 g lard oil, and 2 g cholesterol. Control rats were fed normal diet. Rats were killed at 4, 8, 12, 16, 24, 36, and 48 weeks after HFD exposure. Body weight, liver weight, and epididymal fat weight were measured. Serum levels of fasting glucose, triglyceride, cholesterol, alanine aminotransferase (ALT), free fatty acids (FFA), insulin, and tumor necrosis factor-alpha (TNF-α) were determined. Hepatic histology was examined by H&E stain. Hepatic fibrosis was assessed by VG stain and immunohistochemical staining for transforming growth factor beta 1 (TGF-β1), and alpha-smooth-muscle actin (α-SMA). The liver weight and liver index increased from week 4, when hepatic steatosis was also observed. By week 8, the body weight and epididymal fat weight started increasing, which was associated with increased serum levels of FFA, cholesterol, and TNF-α, as well as development of simple fatty liver. The serum ALT level increased from week 12. Steatohepatitis occurred from weeks 12 through 48. Apparent hepatic perisinosodial fibrosis did not occur until week 24, and progressed from week 36 to 48 with insulin resistance. Therefore, this novel model may be potentially useful in NASH study.