Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition
| Autor: | Schuyler O. Sanderson, Gregory J. Gores, Sophie C. Cazanave, Kimberly Viker, Michael Charlton, Andrea L. McConico, Howard Masuoko, Anuradha Krishnan |
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| Rok vydání: | 2011 |
| Předmět: |
Liver Cirrhosis
Nonalcoholic steatohepatitis medicine.medical_specialty Physiology Apoptosis Biology Diet High-Fat Bioinformatics Mice Animal model Non-alcoholic Fatty Liver Disease Fibrosis Physiology (medical) Internal medicine Small animal Nonalcoholic fatty liver disease medicine Animals Hepatology Disease progression Gastroenterology medicine.disease Fatty Liver Disease Models Animal Liver and Biliary Tract Liver metabolism Endocrinology Liver Disease Progression Unfolded Protein Response Liver pathology |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 301:G825-G834 |
| ISSN: | 1522-1547 0193-1857 |
| Popis: | Although there are small animal platforms that recapitulate some of the histological features of nonalcoholic fatty liver disease, there are no small animal models of nonalcoholic steatohepatitis (NASH) with consistent hepatocellular ballooning and progressive fibrosis that also exhibit fidelity to the human condition physiologically. We examined the metabolic and histological effects of a diet on the basis of the composition of “fast food” (high saturated fats, cholesterol, and fructose). Mice ( n = 8 in each group) were assigned to diets as follows: 1) standard chow (SC), i.e., 13% energy as fat [1% saturated fatty acids (SFA)], 2) high fat (HF), i.e., 60% energy as fat (1% SFA), and 3) fast food (FF), i.e., 40% energy as fat (12% SFA, 2% cholesterol). All three diets were supplemented with high fructose. All diets produced obesity. The HF and FF diets produced insulin resistance. Liver histology was normal in animals fed the SC diet. Steatohepatitis with pronounced ballooning and progressive fibrosis (stage 2) was observed in mice fed the FF diet. Although the HF diet produced obesity, insulin resistance, and some steatosis; inflammation was minimal, and there was no increase in fibrosis. The FF diet produced a gene expression signature of increased fibrosis, inflammation, and endoplasmic reticulum stress and lipoapoptosis. A diet based on high cholesterol, high saturated fat, and high fructose recapitulates features of the metabolic syndrome and NASH with progressive fibrosis. This represents a novel small animal model of fibrosing NASH with high fidelity to the human condition. These results highlight the contribution of dietary composition to the development of nonalcoholic fatty liver disease and NASH. |
| Databáze: | OpenAIRE |
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