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The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and NASH when fed a Western diet supplemented with fructose.
BMC Gastroenterol. 2019 Mar 18; 19(1):41.BG

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.

Authors+Show Affiliations

Crown Bioscience Taicang Inc, Taicang, China.Crown Bioscience Indiana Inc, Indianapolis, USA.Crown Bioscience Indiana Inc, Indianapolis, USA.Crown Bioscience Taicang Inc, Taicang, China.Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.Crown Bioscience Indiana Inc, Indianapolis, USA.Crown Bioscience Indiana Inc, Indianapolis, USA. rpeterson@crownbio.com.Crown Bioscience Taicang Inc, Taicang, China. yxwang@crownbio.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30885145

Citation

Sun, Gao, et al. "The FATZO Mouse, a Next Generation Model of Type 2 Diabetes, Develops NAFLD and NASH when Fed a Western Diet Supplemented With Fructose." BMC Gastroenterology, vol. 19, no. 1, 2019, p. 41.
Sun G, Jackson CV, Zimmerman K, et al. The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and NASH when fed a Western diet supplemented with fructose. BMC Gastroenterol. 2019;19(1):41.
Sun, G., Jackson, C. V., Zimmerman, K., Zhang, L. K., Finnearty, C. M., Sandusky, G. E., Zhang, G., Peterson, R. G., & Wang, Y. J. (2019). The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and NASH when fed a Western diet supplemented with fructose. BMC Gastroenterology, 19(1), 41. https://doi.org/10.1186/s12876-019-0958-4
Sun G, et al. The FATZO Mouse, a Next Generation Model of Type 2 Diabetes, Develops NAFLD and NASH when Fed a Western Diet Supplemented With Fructose. BMC Gastroenterol. 2019 Mar 18;19(1):41. PubMed PMID: 30885145.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and NASH when fed a Western diet supplemented with fructose. AU - Sun,Gao, AU - Jackson,Charles V, AU - Zimmerman,Karen, AU - Zhang,Li-Kun, AU - Finnearty,Courtney M, AU - Sandusky,George E, AU - Zhang,Guodong, AU - Peterson,Richard G, AU - Wang,Yi-Xin Jim, Y1 - 2019/03/18/ PY - 2018/07/03/received PY - 2019/02/27/accepted PY - 2019/3/20/entrez PY - 2019/3/20/pubmed PY - 2019/4/16/medline KW - FATZO mouse KW - Liver disease KW - Metabolic disease KW - NAFLD KW - NASH SP - 41 EP - 41 JF - BMC gastroenterology JO - BMC Gastroenterol VL - 19 IS - 1 N2 - 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. SN - 1471-230X UR - https://www.unboundmedicine.com/medline/citation/30885145/The_FATZO_mouse_a_next_generation_model_of_type_2_diabetes_develops_NAFLD_and_NASH_when_fed_a_Western_diet_supplemented_with_fructose_ L2 - https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-019-0958-4 DB - PRIME DP - Unbound Medicine ER -