Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition
Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition
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DOI：
10.1152/ajpgi.00145.2011
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发表时间：
2011-11-01
影响因子：
4.5
通讯作者：
Gores, Gregory
中科院分区：
文献类型：
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作者：
Charlton, Michael;Krishnan, Anuradha;Gores, Gregory
Charlton M, Krishnan A, Viker K, Sanderson S, Cazanave S, McConico A, Masuoko H, Gores G.快餐饮食小鼠：具有气球化，进行性纤维化和高生理保真度的NASH小动物模型。[J] .中国生物医学工程学报，2011,31(2):825- 834。首次发表于2011年8月11日；doi: 10.1152 / ajpgi.00145.2011。尽管有小动物模型概括了非酒精性脂肪性肝病的一些组织学特征，但没有具有一致的肝细胞气球化和进行性纤维化的非酒精性脂肪性肝炎（NASH）的小动物模型在生理上也表现出对人类状况的保真性。我们以“快餐”的成分（高饱和脂肪、胆固醇和果糖）为基础，研究了饮食对代谢和组织学的影响。每组8只小鼠分别饲喂：1)标准饲料（SC），即13%能量转化为脂肪[1%饱和脂肪酸（SFA）]; 2)高脂肪饲料（HF），即60%能量转化为脂肪（1% SFA）； 3)快餐食品（FF），即40%能量转化为脂肪（12% SFA， 2%胆固醇）。三种饮食都添加了高果糖。所有的饮食都会导致肥胖。HF和FF组产生胰岛素抵抗。饲喂SC日粮的动物肝脏组织学正常。在饲喂FF日粮的小鼠中观察到脂肪性肝炎伴明显的水肿和进行性纤维化（2期）。虽然HF饮食导致肥胖、胰岛素抵抗和一些脂肪变性；炎症轻微，纤维化无增加。FF日粮产生了纤维化、炎症、内质网应激和脂肪凋亡增加的基因表达特征。以高胆固醇、高饱和脂肪和高果糖为基础的饮食概括了代谢综合征和NASH伴进行性纤维化的特征。这代表了一种新颖的小动物纤维化NASH模型，与人类状况高度吻合。这些结果强调了饮食成分对非酒精性脂肪性肝病和NASH发展的贡献。
Charlton M, Krishnan A, Viker K, Sanderson S, Cazanave S, McConico A, Masuoko H, Gores G. 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 301: G825-G834, 2011. First published August 11, 2011; doi: 10.1152/ajpgi.00145.2011.-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.