Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease.
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.
Hong
Feng
F
Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Radaeva
Svetlana
S
Pan
Hong-na
HN
Tian
Zhigang
Z
Veech
Richard
R
Gao
Bin
B
D000818:Animals; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D015536:Down-Regulation; D000431:Ethanol / Q000494:pharmacology; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy / Q000378:metabolism; D015870:Gene Expression; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications; D010084:Oxidation-Reduction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D002492:Central Nervous System Depressants; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D015850:Interleukin-6; D018160:Receptors, Cytoplasmic and Nuclear; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol