title: Amelioration of high fat diet induced liver lipogenesis and hepatic steatosis by interleukin-22.
abstract: OBJECTIVE
  Interleukin-22 (IL-22) is a Th17-related cytokine within the IL-10 family and plays an important role in host defense and inflammatory responses in orchestration with other Th17 cytokines. IL-22 exerts its functions in non-immune cells as its functional receptor IL-22R1 is restricted in peripheral tissues but not in immune cells. It was recently found that IL-22 serves as a protective molecule to counteract the destructive nature of the T cell-mediated immune response to liver damage. However, it is currently unknown whether IL-22 has an effect on lipid metabolism in the liver.
  
  
  METHODS
  In this study, we demonstrate that IL-22 alleviates hepatic steatosis induced by high fat diet (HFD).
  
  
  RESULTS
  Administration of recombinant murine IL-22 (rmIL-22) was able to stimulate STAT3 phosphorylation in HepG2 cells and mouse liver. The activation of STAT3 by rmIL-22 was reduced by the over-expression of a dominant negative IL-22R1. Within hours after rmIL-22 treatment, the expression of lipogenesis-related genes including critical transcription factors and enzymes for lipid synthesis in the liver was significantly down-regulated. The levels of triglyceride and cholesterol in the liver were significantly reduced by long-term treatment of rmIL-22 in C57BL/6 and ob/ob mice fed with HFD. The HFD-induced increases of ALT and AST in ob/ob mice were ameliorated by rmIL-22 treatment. In addition, the expression of fatty acid synthase and TNF-alpha in the liver was decreased by long-term rmIL-22 administration.
  
  
  CONCLUSIONS
  Collectively, these data indicate that IL-22, in addition to its known functions in host defense and inflammation, has a protective role in HFD-induced hepatic steatosis via its regulation on lipid metabolism in the liver.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lingdi
authors.initials: L
authors.lastname: Wang
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Fan
authors.forename: Lu
authors.initials: L
authors.lastname: Zhu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Li
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Ruan
authors.forename: Heng
authors.initials: H
authors.lastname: Huang
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Huang
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007378:Interleukins / Q000494:pharmacology* / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D002784:Cholesterol; D004041:Dietary Fats; D007378:Interleukins; D050796:STAT3 Transcription Factor; D014280:Triglycerides; D000097043:Interleukin-22; C494087:Stat3 protein, mouse