Medaka as a model for human nonalcoholic steatohepatitis
Medaka as a model for human nonalcoholic steatohepatitis
复制标题
DOI：
10.1242/dmm.002311
复制
发表时间：
2010-07-01
影响因子：
4.3
通讯作者：
Sakaida, Isao
中科院分区：
文献类型：
--
作者：
Matsumoto, Toshihiko;Terai, Shuji;Sakaida, Isao
非酒精性脂肪性肝炎（NASH）的全球发病率正在上升，目前的NASH哺乳动物模型尚不完善。我们在米鱼（Oryzias latipes）中建立了一个NASH模型，该模型基于给鱼喂食高脂肪饮食（HFD）。饲喂HFD （HFD- Medaka）的Medaka表现出高脂血症和高血糖症，肝脏组织学检查显示气球变性。脂肪生成基因SREBP-1c、FAS和ACC1表达升高，而脂溶基因PPARA和CPT1表达降低。肝脏脂肪酸组成方面，n-3多不饱和脂肪酸（PUFAs）和n-6多不饱和脂肪酸浓度下降，n-3: n-6比值降低。用n-3 PUFA二十碳五烯酸（EPA）治疗HFD-medaka减轻了疾病，通过恢复正常的肝脏脂肪酸组成和正常的脂肪生成和脂肪分解基因表达水平来判断。此外，被喂食缺乏n-3 PUFAs的饮食的medaka出现了NASH特征。因此，HFD可以在鳉鱼中诱导NASH，肝脏中n-3 PUFAs的比例影响这些鱼NASH病理的进展。我们的模型应该被证明有助于解剖人类NASH的原因和设计新的有效治疗方法。
The global incidence of nonalcoholic steatohepatitis (NASH) is increasing and current mammalian models of NASH are imperfect. We have developed a NASH model in the ricefish medaka (Oryzias latipes), which is based on feeding the fish a high-fat diet (HFD). Medaka that are fed a HFD (HFD-medaka) exhibited hyperlipidemia and hyperglycemia, and histological examination of the liver revealed ballooning degeneration. The expression of lipogenic genes (SREBP-1c, FAS and ACC1) was increased, whereas the expression of lipolytic genes (PPARA and CPT1) was decreased. With respect to liver fatty acid composition, the concentrations of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs had declined and the n-3: n-6 ratio was reduced. Treatment of HFD-medaka with the n-3 PUFA eicosapentaenoic acid (EPA) mitigated disease, as judged by the restoration of normal liver fatty acid composition and normal expression levels of lipogenic and lipolytic genes. Moreover, medaka that were fed a diet deficient in n-3 PUFAs developed NASH features. Thus, NASH can be induced in medaka by a HFD, and the proportion of n-3 PUFAs in the liver influences the progress of NASH pathology in these fish. Our model should prove helpful for the dissection of the causes of human NASH and for the design of new and effective therapies.