Effect of dietary fat to produce non-alcoholic fatty liver in the rat
Effect of dietary fat to produce non-alcoholic fatty liver in the rat
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DOI：
10.1111/j.1440-1746.2009.05870.x
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发表时间：
2009-08-01
影响因子：
4.1
通讯作者：
Oates, Phillip S.
中科院分区：
文献类型：
--
作者：
Ahmed, Umbreen;Redgrave, Trevor G.;Oates, Phillip S.
背景和目的：非酒精性脂肪性肝炎（NASH）属于非酒精性脂肪性肝病（NAFLD）的一个谱系。氧化应激被假设在疾病的进展中起重要作用。我们使用的Lieber/DeCarli模型NASH.Methods：雄性Sprague-Dawley大鼠喂养标准（35%的能量来自脂肪）或高脂肪（71%的能量来自脂肪）流质饮食，自由或三分之二的量消耗自由最初为3周，然后延长到5 weeks.Results：脂肪变性是不存在的大鼠在3周喂养，但5周，高脂肪/自由组显示微泡脂肪变性和大泡脂肪变性病灶无炎症。血清谷草转氨酶（AST）和丙氨酸转氨酶（ALT）水平无差异。喂养5周时，高脂自由组的肝脏甘油三酯最高，自由组高于限制组。与高脂自由进食组相比，标准自由进食组的氧化应激标志物羟烯醛（HAE）降低。肝mRNA的白细胞介素-6，血红素加氧酶-1，和标记物的内质网应激：C/EBP同源蛋白（CHOP），葡萄糖反应蛋白-78（GRP 78）和剪接的X-box DNA结合蛋白（剪接的XBP 1）是类似的在adlibgroups.Conclusions：延长喂养期的高脂肪/自由采食5周放置我们的大鼠与I型到II型NAFLD相比，更先进的III型状态以前获得3周喂养后。获得的较温和的条件提高了我们的大鼠中存在的抵抗疾病进展的遗传修饰剂的前景。
Background and Aim:Non-alcoholic steatohepatitis (NASH) belongs to a spectrum of non-alcoholic fatty liver disease (NAFLD). Oxidative stress is hypothesized to play an important role in the progression of the disease. We used the Lieber/DeCarli model for NASH to investigate the mechanisms involved in its progression.Methods:Male Sprague-Dawley rats were fed standard (35% of energy from fat) or high fat (71% of energy from fat) liquid diets, ad libitum or two-thirds of the amount consumed ad libitum initially for 3 weeks and then extended to 5 weeks.Results:Steatosis was absent in rats at 3 weeks feeding, but by 5 weeks, the high fat/ad lib group showed microvesicular steatosis and foci of macrovesicular steatosis without inflammation. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were not different. By 5 weeks feeding, hepatic triglycerides were highest in the high fat ad lib group and the ad lib groups were higher compared with their restricted groups. The oxidative stress marker, hydroxyalkenal (HAE) was decreased in the standard ad lib compared with the high fat ad lib group. Liver mRNA of interleukin-6, haem oxygenase-1, and markers of endoplasmic stress: C/EBP homologous protein (CHOP), glucose responsive protein-78 (GRP78) and spliced X-box DNA binding protein (spliced XBP1) were similar in the ad lib groups.Conclusions:Extending the feeding period of the high fat/ad lib diet for 5 weeks placed our rats with Type I to II NAFLD compared to the more progressed Type III state previously obtained after 3 weeks feeding. The milder condition obtained raised the prospect of genetic modifiers present in our rats that resist disease progression.