The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and NASH when fed a Western diet supplemented with fructose
| العنوان: | The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and NASH when fed a Western diet supplemented with fructose |
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| المؤلفون: | Courtney Finnearty, Charles V. Jackson, Yixin Wang, Karen M. Zimmerman, Richard G. Peterson, Guodong Zhang, George E. Sandusky, Li-Kun Zhang, Gao Sun |
| المصدر: | BMC Gastroenterology BMC Gastroenterology, Vol 19, Iss 1, Pp 1-11 (2019) |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Metabolic disease, Fructose, Type 2 diabetes, Diet, High-Fat, digestive system, High cholesterol, Mice, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Insulin resistance, Non-alcoholic Fatty Liver Disease, FATZO mouse, NAFLD, Internal medicine, Animals, Medicine, Obesity, lcsh:RC799-869, business.industry, Fatty liver, NASH, Gastroenterology, nutritional and metabolic diseases, General Medicine, medicine.disease, digestive system diseases, Disease Models, Animal, Endocrinology, Diabetes Mellitus, Type 2, Liver, Diet, Western, Sweetening Agents, 030220 oncology & carcinogenesis, Disease Progression, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, Liver function, Steatosis, Steatohepatitis, business, Research Article |
| الوصف: | Background Metabolic disorders such as insulin resistance, obesity, and hyperglycemia are prominent risk factors for the development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH). Dietary rodent models employ high fat, high cholesterol, high fructose, methionine/choline deficient diets or combinations of these to induce NAFLD/NASH. The FATZO mice spontaneously develop the above metabolic disorders and type 2 diabetes (T2D) when fed with a normal chow diet. The aim of the present study was to determine if FATZO mice fed a high fat and fructose diet would exacerbate the progression of NAFLD/NASH. Methods Male FATZO mice at the age of 8 weeks were fed with high fat Western diet (D12079B) supplemented with 5% fructose in the drinking water (WDF) for the duration of 20 weeks. The body weight, whole body fat content, serum lipid profiles and liver function markers were examined monthly along with the assessment of liver histology for the development of NASH. In addition, the effects of obeticholic acid (OCA, 30 mg/kg, QD) on improvement of NASH progression in the model were evaluated. Results Compared to normal control diet (CD), FATZO mice fed with WDF were heavier with higher body fat measured by qNMR, hypercholesterolemia and had progressive elevations in AST (~ 6 fold), ALT (~ 6 fold), liver over body weight (~ 2 fold) and liver triglyceride (TG) content (1.4–2.9 fold). Histological examination displayed evidence of NAFLD/NASH, including hepatic steatosis, lobular inflammation, ballooning and fibrosis in FATZO mice fed WDF. Treatment with OCA for 15 weeks in FATZO mice on WDF significantly alleviated hypercholesterolemia and elevation of AST/ALT, reduced liver weight and liver TG contents, attenuated hepatic ballooning, but did not affect body weight and blood TG levels. Conclusion WDF fed FATZO mice represent a new model for the study of progressive NAFLD/NASH with concurrent metabolic dysregulation. |
| تدمد: | 1471-230X |
| DOI: | 10.1186/s12876-019-0958-4 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::01d5e5aec897049aae466b28bb6f2a5a https://doi.org/10.1186/s12876-019-0958-4 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....01d5e5aec897049aae466b28bb6f2a5a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1471230X |
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| DOI: | 10.1186/s12876-019-0958-4 |