Department of Nutrition and Food Sciences, Texas Woman's University, Denton, USA.
J Nutr Biochem. 2011 Oct;22(10):979-84. doi: 10.1016/j.jnutbio.2010.08.011. Epub 2010 Dec 28.
Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of the growing metabolic syndrome epidemic that could progress to cirrhosis. Animal models adequately mimicking this condition in humans are scanty.
The objective of our study was to investigate whether high-fat diets (HFD) with adequate methionine and choline levels can induce pathophysiological features typical of human NASH in C57BL/6J mice.
Forty C57BL/6J mice, divided into control and high-fat (HF) groups, were fed low-fat diet and HFD, ad libitum respectively for 20 weeks. At the end of 20 weeks, animals were sacrificed and assays were performed for blood biomarkers typical of human NASH. Adipose tissue depots were collected and liver samples were processed for histological examination.
High-fat feeding led to increased triglyceride accumulation in the liver (8.9 μmol/100 mg liver tissue vs. 2.6 μmol/100 mg for control) and induced histopathological features of human NASH including hepatic steatosis, ballooning inflammation and fibrosis. Expressions of proteins and chemokines predominant in NASH including collagens I, III and IV and platelet derived growth factor (PDGF) A and B were significantly higher in animals fed the HFD. Liver enzymes alanine transaminase, aspartate transaminase and alkaline phosphatase were significantly (P<.05) elevated in the HF group compared to controls. Mice on HFD also developed hyperglycemia, hyperinsulinemia, hypoadiponectinemia along with elevated tumor necrosis factor α, resistin, leptin, free fatty acids, transforming growth factor β and malondialdehyde levels that characterize NASH in humans.
Long-term HF feeding with adequate methionine and choline can induce many of the pathophysiological features typical of human NASH in C57BL/6J mice.
非酒精性脂肪性肝炎（NASH）是代谢综合征流行的肝脏表现，可进展为肝硬化。能够充分模拟人类这种疾病的动物模型很少。
我们的研究目的是探讨高脂肪饮食（HFD）是否能在 C57BL/6J 小鼠中诱导出具有人类 NASH 典型病理生理特征的疾病。
将 40 只 C57BL/6J 小鼠分为对照组和高脂肪（HF）组，分别给予低脂饮食和 HFD 自由喂养 20 周。20 周结束时，处死动物并检测血液生物标志物，这些标志物是人类 NASH 的典型标志物。收集脂肪组织和肝脏样本，进行组织学检查。
高脂肪喂养导致肝脏甘油三酯积累增加（8.9μmol/100mg 肝组织比对照组 2.6μmol/100mg），并诱导出人类 NASH 的组织病理学特征，包括肝脂肪变性、气球样炎症和纤维化。在喂养 HFD 的动物中，NASH 中主要表达的蛋白和趋化因子如 I、III 和 IV 型胶原蛋白和血小板衍生生长因子（PDGF）A 和 B 的表达显著增加。与对照组相比，HF 组的肝脏酶丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶显著升高（P<.05）。HFD 喂养的小鼠还出现了高血糖、高胰岛素血症、脂联素水平降低，同时肿瘤坏死因子-α、抵抗素、瘦素、游离脂肪酸、转化生长因子-β和丙二醛水平升高，这些都是人类 NASH 的特征。
长期给予充足蛋氨酸和胆碱的高脂肪饮食可以在 C57BL/6J 小鼠中诱导出许多具有人类 NASH 典型病理生理特征的疾病。
