Zhang Linqiang, Zhang Zhiguo, Li Yunhai, Liao Shasha, Wu Xiaoyun, Chang Qing, Liang Bin
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science &Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
Sci Rep. 2015 Nov 2;5:15970. doi: 10.1038/srep15970.
Animal models are indispensible to investigate the pathogenesis and treatments of non-alcoholic fatty liver diseases (NAFLD). Altered cholesterol metabolism has been implicated into the pathogenesis of NAFLD. Here, using high fat, cholesterol and cholate diet (HFHC), we generated a novel tree shrew (Tupaia belangeri chinensis) model of NAFLD, which displayed dyslipidemia with increased levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and high density lipoprotein-cholesterol (HDL-c), but decreased level of triglycerides (TG). Liver histopathology and genes expression indicated that HFHC diet successfully induced liver steatosis to inflammation and fibrosis progressively within 10 weeks. Moreover, HFHC induced the transcriptional expression of lipoprotein lipase (lpl) in the liver, but repressed the expression of LDL receptor, and the endogenous synthesis pathway and excretion of cholesterol. Notably, Poloxamer 407 (P-407) inhibition of LPL improved the severity of steatosis and reduced inflammation. These results illustrated that LPL plays an important role in cholesterol metabolism in NAFLD, and the tree shrew may be a valuable animal model for further research into NAFLD.
动物模型对于研究非酒精性脂肪性肝病（NAFLD）的发病机制和治疗方法至关重要。胆固醇代谢改变与NAFLD的发病机制有关。在此，我们使用高脂、高胆固醇和高胆酸盐饮食（HFHC）建立了一种新的树鼩（Tupaia belangeri chinensis）NAFLD模型，该模型表现为血脂异常，血浆丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-c）和高密度脂蛋白胆固醇（HDL-c）水平升高，但甘油三酯（TG）水平降低。肝脏组织病理学和基因表达表明，HFHC饮食在10周内成功地将肝脏脂肪变性逐步诱导为炎症和纤维化。此外，HFHC诱导肝脏中脂蛋白脂肪酶（lpl）的转录表达，但抑制低密度脂蛋白受体的表达以及胆固醇的内源性合成途径和排泄。值得注意的是，泊洛沙姆407（P-407）对LPL的抑制作用改善了脂肪变性的严重程度并减轻了炎症。这些结果表明，LPL在NAFLD的胆固醇代谢中起重要作用，树鼩可能是进一步研究NAFLD的有价值的动物模型。
