Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings, ranging from simple fatty liver through non-alcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance. Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models. The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages. Within the past several years, great emphasis has been placed on the development of an appropriate model for human NASH. This paper reviews the widely used experimental models of NAFLD in rats. We discuss nutritional, genetic and combined models of NAFLD and their pros and cons. The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies. Considering the legislative, ethical, economical and health factors of NAFLD, animal models are essential tools for the research of this disease.

• Keywords
• Animal model, High-fat diet, Methionine- and choline-deficient diet, Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, Otsuka-Long-Evans-Tokushima fatty rats, Zucker rats,
• MeSH
• Species Specificity MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Liver Cirrhosis metabolism   pathology   physiopathology   MeSH
• Liver metabolism   pathology   physiopathology   MeSH
• Rats MeSH
• Humans MeSH
• Disease Models, Animal * MeSH
• Non-alcoholic Fatty Liver Disease * etiology   genetics   metabolism   pathology   physiopathology   MeSH
• Nutritional Status MeSH
• Disease Progression MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Oxidative stress and mitochondrial dysfunction play an important role in the pathogenesis of nonalcoholic fatty liver disease and toxic liver injury. The present study was designed to evaluate the effect of exogenous inducer of oxidative stress (tert-butyl hydroperoxide, tBHP) on nonfatty and steatotic hepatocytes isolated from the liver of rats fed by standard and high-fat diet, respectively. In control steatotic hepatocytes, we found higher generation of ROS, increased lipoperoxidation, an altered redox state of glutathione, and decreased ADP-stimulated respiration using NADH-linked substrates, as compared to intact lean hepatocytes. Fatty hepatocytes exposed to tBHP exert more severe damage, lower reduced glutathione to total glutathione ratio, and higher formation of ROS and production of malondialdehyde and are more susceptible to tBHP-induced decrease in mitochondrial membrane potential. Respiratory control ratio of complex I was significantly reduced by tBHP in both lean and steatotic hepatocytes, but reduction in NADH-dependent state 3 respiration was more severe in fatty cells. In summary, our results collectively indicate that steatotic rat hepatocytes occur under conditions of enhanced oxidative stress and are more sensitive to the exogenous source of oxidative injury. This confirms the hypothesis of steatosis being the first hit sensitizing hepatocytes to further damage.

• MeSH
• Diet, High-Fat MeSH
• Glutathione metabolism   MeSH
• Hepatocytes drug effects   metabolism   MeSH
• Rats MeSH
• Cells, Cultured MeSH
• L-Lactate Dehydrogenase metabolism   MeSH
• Malondialdehyde metabolism   MeSH
• Membrane Potential, Mitochondrial drug effects   MeSH
• Non-alcoholic Fatty Liver Disease metabolism   pathology   MeSH
• Oxidative Stress drug effects   MeSH
• Lipid Peroxidation drug effects   MeSH
• Rats, Wistar MeSH
• Reactive Oxygen Species metabolism   MeSH
• tert-Butylhydroperoxide toxicity   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Glutathione MeSH
• L-Lactate Dehydrogenase MeSH
• Malondialdehyde MeSH
• Reactive Oxygen Species MeSH
• tert-Butylhydroperoxide MeSH

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic condition of the liver in the western world. There is only little evidence about altered sensitivity of steatotic liver to acute toxic injury. The aim of this project was to test whether hepatic steatosis sensitizes rat liver to acute toxic injury induced by thioacetamide (TAA). Male Sprague-Dawley rats were fed ad libitum a standard pelleted diet (ST-1, 10% energy fat) and high-fat gelled diet (HFGD, 71% energy fat) for 6 weeks and then TAA was applied intraperitoneally in one dose of 100 mg/kg. Animals were sacrificed in 24-, 48- and 72-h interval after TAA administration. We assessed the serum biochemistry, the hepatic reduced glutathione, thiobarbituric acid reactive substances, cytokine concentration, the respiration of isolated liver mitochondria and histopathological samples (H+E, Sudan III, bromodeoxyuridine [BrdU] incorporation). Activities of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and concentration of serum bilirubin were significantly higher in HFGD groups after application of TAA, compared to ST-1. There were no differences in activities of respiratory complexes I and II. Serum tumour necrosis factor alpha at 24 and 48 h, liver tissue interleukin-6 at 72 h and transforming growth factor β1 at 24 and 48 h were elevated in TAA-administrated rats fed with HFGD, but not ST-1. TAA-induced centrilobular necrosis and subsequent regenerative response of the liver were higher in HFGD-fed rats in comparison with ST-1. Liver affected by NAFLD, compared to non-steatotic liver, is more sensitive to toxic effect of TAA.

• MeSH
• Cholesterol metabolism   MeSH
• Cytokines blood   MeSH
• Dietary Fats adverse effects   MeSH
• Liver drug effects   metabolism   pathology   MeSH
• Carcinogens toxicity   MeSH
• Rats MeSH
• Thiobarbituric Acid Reactive Substances metabolism   MeSH
• Disease Models, Animal MeSH
• Non-alcoholic Fatty Liver Disease MeSH
• Rats, Sprague-Dawley MeSH
• Cell Proliferation drug effects   MeSH
• Electron Transport Complex I drug effects   physiology   MeSH
• Electron Transport Complex II drug effects   physiology   MeSH
• Thioacetamide toxicity   MeSH
• Triglycerides metabolism   MeSH
• Fatty Liver blood   chemically induced   pathology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Cholesterol MeSH
• Cytokines MeSH
• Dietary Fats MeSH
• Carcinogens MeSH
• Thiobarbituric Acid Reactive Substances MeSH
• Electron Transport Complex I MeSH
• Electron Transport Complex II MeSH
• respiratory complex II MeSH Browser
• Thioacetamide MeSH
• Triglycerides MeSH