Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease
Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease
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DOI：
10.1002/hep.20400
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发表时间：
2004-10-01
期刊：
影响因子：
13.5
通讯作者：
Gao, B
中科院分区：
文献类型：
--
作者：
Hong, F;Radaeva, S;Gao, B
脂肪肝以往主要与过量饮酒有关，现在也被认为是肥胖的一种并发症，并且是包括缺血/再灌注损伤在内的更严重肝脏病理形式的重要前期状态。目前尚无治疗脂肪肝的标准方案。因此，我们在3种脂肪肝小鼠模型中检测了注射白细胞介素6（IL - 6）10天的效果：瘦素缺乏的ob/ob小鼠、喂食乙醇的小鼠以及喂食高脂肪饮食的小鼠。在所有3种模型中，注射IL - 6减少了脂肪变性，并使血清氨基转移酶恢复正常。体内IL - 6治疗的有益效果部分源于脂肪酸的线粒体β氧化增加以及肝脏中甘油三酯和胆固醇的输出增加。然而，给分离培养的脂肪变性肝细胞施用IL - 6未能降低脂质含量，这表明体内IL - 6的有益效果并非仅仅源于其对肝细胞的作用。IL - 6治疗增加了肝脏过氧化物酶体增殖物激活受体（PPAR）α，并降低了肝脏和血清肿瘤坏死因子（TNF）α。最后，用IL - 6治疗10天可防止脂肪肝对热缺血/再灌注损伤的易感性。总之，长期施用IL - 6可改善脂肪肝并防止热缺血/再灌注性脂肪肝损伤，这表明IL - 6在治疗人类脂肪肝疾病方面具有治疗潜力。
Fatty liver, formerly associated predominantly with excessive alcohol intake, is now also recognized as a complication of obesity and an important precursor state to more severe forms of liver pathology including ischemia/reperfusion injury. No standard protocol for treating fatty liver exists at this time. We therefore examined the effects of 10 days of interleukin 6 (IL-6) injection in 3 murine models of fatty liver: leptin deficient ob/ob mice, ethanol-fed mice, and mice fed a high-fat diet. In all 3 models, IL-6 injection decreased steatosis and normalized serum aminotransferase. The beneficial effects of IL-6 treatment in vivo resulted in part from an increase in mitochondrial beta oxidation of fatty acid and an increase in hepatic export of triglyceride and cholesterol. However, administration of IL-6 to isolated cultured steatotic hepatocytes failed to decrease lipid contents, suggesting that the beneficial effects of IL-6 in vivo do not result from its effects on hepatocytes alone. IL-6 treatment increased hepatic peroxisome proliferator-activated receptor (PPAR) alpha and decreased liver and serum tumor necrosis factor (TNF) alpha. Finally, 10 days of treatment with IL-6 prevented the susceptibility of fatty livers to warm ischemia/reperfusion injury. In conclusion, long-term IL-6 administration ameliorates fatty livers and protects against warm ischemia/reperfusion fatty liver injury, suggesting the therapeutic potential of IL-6 in treating human fatty liver disease.