Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease

Authors

  • Feng Hong,

    1. Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD
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  • Svetlana Radaeva,

    1. Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD
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  • Hong-Na Pan,

    1. Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD
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  • Zhigang Tian,

    1. Institute of Immunology, School of Life Science, University of Science and Technology of China, Hefei, Anhui, China
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  • Richard Veech,

    1. Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD
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  • Bin Gao M.D., PhD.

    Corresponding author
    1. Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD
    • Section on Liver Biology, NIAAA/NIH, Park Bldg. Rm. 120, 12420 Parklawn Drive, MSC 8115, Bethesda, MD 20892
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Abstract

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 indluding 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 β 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) α and decreased liver and serum tumor necrosis factor (TNF) α. 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). (Hepatology 2004;40:933–941).

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