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Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition.
Am J Physiol Gastrointest Liver Physiol. 2011 Nov; 301(5):G825-34.AJ

Abstract

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.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. charlton.michael@mayo.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21836057

Citation

Charlton, Michael, et al. "Fast Food Diet Mouse: Novel Small Animal Model of NASH With Ballooning, Progressive Fibrosis, and High Physiological Fidelity to the Human Condition." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 301, no. 5, 2011, pp. G825-34.
Charlton M, Krishnan A, Viker K, et al. Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G825-34.
Charlton, M., Krishnan, A., Viker, K., Sanderson, S., Cazanave, S., McConico, A., Masuoko, H., & Gores, G. (2011). Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition. American Journal of Physiology. Gastrointestinal and Liver Physiology, 301(5), G825-34. https://doi.org/10.1152/ajpgi.00145.2011
Charlton M, et al. Fast Food Diet Mouse: Novel Small Animal Model of NASH With Ballooning, Progressive Fibrosis, and High Physiological Fidelity to the Human Condition. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G825-34. PubMed PMID: 21836057.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition. AU - Charlton,Michael, AU - Krishnan,Anuradha, AU - Viker,Kimberly, AU - Sanderson,Schuyler, AU - Cazanave,Sophie, AU - McConico,Andrea, AU - Masuoko,Howard, AU - Gores,Gregory, Y1 - 2011/08/11/ PY - 2011/8/13/entrez PY - 2011/8/13/pubmed PY - 2011/12/16/medline SP - G825 EP - 34 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am. J. Physiol. Gastrointest. Liver Physiol. VL - 301 IS - 5 N2 - 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. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/21836057/Fast_food_diet_mouse:_novel_small_animal_model_of_NASH_with_ballooning_progressive_fibrosis_and_high_physiological_fidelity_to_the_human_condition_ L2 - http://journals.physiology.org/doi/full/10.1152/ajpgi.00145.2011?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -