Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice
Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice
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DOI：
10.1016/j.bbrc.2006.02.032
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发表时间：
2006-04-21
影响因子：
3.1
通讯作者：
Farrell, GC
中科院分区：
文献类型：
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作者：
Arsov, T;Larter, CZ;Farrell, GC
单纯性脂肪变性、良性肝病和非酒精性脂肪性肝炎之间的生化差异。导致肝硬化的原因尚不清楚肥胖的澳大利亚人是一种在Alms 1基因中有截断突变（foz）的肥胖小鼠。喂食食物的雌性foz/foz小鼠出现肥胖、糖尿病和单纯性脂肪变性。我们给foz/foz和野生型小鼠喂食高脂肪食物。Foz/foz小鼠出现血清ALT升高和重度脂肪性肝炎，伴肝细胞气球样变、炎症和纤维化;野生型小鼠表现为单纯性脂肪变性。有利于肝细胞脂质积累（鼠酸摄取：脂肪生成）和脂质处置（脂肪酸β-氧化;甘油三酯排出）的生化途径都是由野生型高脂喂养诱导的，但foz/foz小鼠没有。由此产生的极高的肝脏甘油三酯水平与诱导线粒体解偶联蛋白-2和脂肪细胞特异性脂肪酸结合蛋白-2，但不是细胞色素P4502 el或脂质过氧化。在这个代谢综合征模型中，脂肪变性向脂肪性肝炎的转变与低脂联素血症有关，低脂联素血症是肝脏脂肪酸处理途径的介导物。(c)2006年爱思唯尔公司All rights reserved.
The biochemical differences between simple steatosis, a benign liver disease, and non-alcoholic steatohepatitis. which leads to cirrhosis, are unclear. Fat aussie is an obese mouse strain with a truncating mutation (foz) in the Alms1 gene. Chow-fed female foz/foz mice develop obesity, diabetes, and simple steatosis. We fed foz/foz and wildtype mice a high-fat diet. Foz/foz mice developed serum ALT elevation and severe steatohepatitis with hepatocyte ballooning, inflammation, and fibrosis; wildtype mice showed simple steatosis. Biochemical pathways favoring hepatocellular lipid accumulation (ratty acid uptake: lipogenesis) and lipid disposal (fatty acid beta-oxidation; triglyceride egress) were both induced by high-fat feeding in wildtype but not foz/foz mice. The resulting extremely high hepatic triglyceride levels were associated with induction of mitochondrial uncoupling protein-2 and adipocyte-specific fatty acid binding protein-2, but not cytochrome P4502el or lipid peroxidation. In this model of metabolic syndrome, transition of steatosis to steatohepatitis was associated with hypoadiponectinemia, a mediator of hepatic fatty acid disposal pathways. (c) 2006 Elsevier Inc. All rights reserved.