Complement C3 contributes to ethanol-induces liver steatosis in mice
Complement C3 contributes to ethanol-induces liver steatosis in mice
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DOI：
10.1080/07853890600664608
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
Meri, Seppo
中科院分区：
文献类型：
--
作者：
Bykov, Igor;Junnikkala, Sami;Meri, Seppo
背景越来越清楚的是，肝脏脂肪变性是酒精暴露的典型早期后果，使肝脏对更严重的炎症和纤维化变化敏感。另一方面，关键补体成分C3的激活，在引起炎症和组织损伤的核心球员，也被称为参与脂质代谢的调节。这促使我们研究缺乏C3（C3-/-）的小鼠酒精性肝脂肪变性的发展。给C3-/-和正常C3+/+小鼠喂食含或不含乙醇的促进脂肪变性的高脂肪饮食6周。不含乙醇的饮食在C3-/-小鼠中引起中度肝脏脂肪变性，但在C3+/+小鼠中没有。正如预期的那样，含乙醇的饮食导致C3+/+小鼠中显著的大泡性脂肪变性并增加肝脏甘油三酯含量。相比之下，乙醇饮食倾向于减少脂肪变性，对C3-/-小鼠的肝脏甘油三酯没有进一步的影响。此外，虽然在正常小鼠中乙醇显着增加肝/体重比，肝丙二醛水平和血清丙氨酸氨基转移酶（ALT）的活动，这些影响是不存在的或小的C3-/-小鼠。用普通饲料喂养的小鼠进行的单独实验证实了乙醇在C3-/-小鼠中的异常脂肪变性作用：急性给药乙醇后4小时，C3+/+小鼠的肝脏甘油三酯水平增加了138%（P < 0.001），但C3小鼠仅增加了64%（n.s.）。结论在C3-/-小鼠中，酒精诱导的肝脏脂肪变性在慢性或急性酒精暴露后不存在或强烈减少。这表明补体系统及其成分C3有助于酒精诱导的脂肪肝及其后果的发展。
Background. It is becoming increasingly clear that liver steatosis, a typical early consequence of alcohol exposure, sensitizes the liver to more severe inflammatory and fibrotic changes. On the other hand, activation of the key complement component C3, a central player in causing inflammation and tissue damage, is also known to be involved in the regulation of lipid metabolism. This prompted us to study the development of alcoholic liver steatosis in mice lacking C3 (C3-/-).Results. Both C3-/- and normal C3+/+ mice were fed a steatosis-promoting high-fat diet with or without ethanol for 6 weeks. The diet without ethanol caused moderate liver steatosis in C3-/- but not in C3+/+ mice. As expected, ethanol-containing diet caused marked macrovesicular steatosis and increased the liver triglyceride content in C3+/+ mice. In contrast, ethanol diet tended to reduce steatosis and had no further effect on liver triglycerides in C3-/- mice. Furthermore, while in normal mice ethanol significantly increased the liver/body weight ratio, liver malondialdehyde level and serum alanine aminotransferase (ALT) activity, these effects were absent or small in C3-/- mice. A separate experiment with mice on chow diet confirmed the aberrant steatotic effect of ethanol in C3-/- mice: 4 hours after acute dosing of ethanol the liver triglyceride level had increased by 138% in C3+/+ mice (P < 0.001), but only by 64% in C3 mice (n.s.).Conclusion. In C3-/- mice alcohol-induced liver steatosis is absent or strongly reduced after chronic or acute alcohol exposure. This suggests that the complement system and its component C3 contribute to the development of alcohol-induced fatty liver and its consequences.