NDLI: The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and NASH when fed a Western diet supplemented with fructose

Content Provider	Springer Nature : BioMed Central
Author	Sun, Gao Jackson, Charles V. Zimmerman, Karen Zhang, Li-Kun Finnearty, Courtney M. Sandusky, George E. Zhang, Guodong Peterson, Richard G. Wang, Yi-Xin (Jim)
Abstract	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.
Related Links	https://bmcgastroenterol.biomedcentral.com/counter/pdf/10.1186/s12876-019-0958-4.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12876-019-0958-4
Journal	BMC Gastroenterology
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2019-03-18
Access Restriction	Open
Subject Keyword	Gastroenterology Internal Medicine Hepatology Metabolic disease Liver disease NAFLD NASH FATZO mouse
Content Type	Text
Resource Type	Article
Subject	Gastroenterology
Journal Impact Factor	2.5/2023
5-Year Journal Impact Factor	2.7/2023

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