Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease
✍ Scribed by Feng Hong; Svetlana Radaeva; Hong-na Pan; Zhigang Tian; Richard Veech; Bin Gao
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 497 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
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  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) ␣ and decreased liver and serum tumor necrosis factor (TNF) ␣. 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. Supplementary material for this article can be found on the Hepatology website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).