肝脏研究领域的国际权威杂志Journal of Hepatology近日发表了中科院上海生科院营养科学研究所陈雁研究组的最新研究成果。陈雁研究员指导的博士研究生杨玲等揭示了在高脂饮食诱导的脂肪肝动物模型中，白介素-22（IL-22）通过抑制脂肪生成和炎症相关基因的表达对脂肪肝起保护作用。
IL-22是白介素-10家族的成员，除了在Th17细胞中高表达之外，在NK和NKT等细胞中也有表达。以前的研究提示了IL-22在组织损伤修复以及牛皮癣、肝炎、肺炎、肠炎等慢性炎症中发挥重要作用。IL-22的特异性受体表达在免疫系统以外的多种组织。杨玲等的研究首次揭示了IL-22在肝脏脂代谢中的作用。重组的小鼠IL-22蛋白可以快速降低肝脏中脂肪生成相关基因的表达。高脂饮食的C57BL/6小鼠和ob/ob小鼠经过IL-22蛋白的注射，肝脏中的甘油三酯和胆固醇水平显着下降，同时血清转氨酶水平也相应下降。另外肝脏中的TNF-alpha的表达水平也有所降低。这些结果表明IL-22对肝脏脂肪变性具有保护作用，并且该保护作用部分是通过下调脂肪生成相关基因和炎症因子TNF-alpha表达实现的。
炎症反应与代谢调控有着共同的信号通路，越来越多的炎症相关基因被发现参与代谢综合症的致病过程。该研究提示IL-22是继IL-6和IL-10之后又一个参与炎症反应和代谢调控的细胞因子，IL-22有可能成为干预脂肪肝发生发展的新手段。
生物谷推荐原文出处：
Journal of Hepatology doi:10.1016/j.jhep.2010.03.004
Amelioration of high fat diet induced liver lipogenesis and hepatic steatosis by interleukin-22
Ling Yang1, Yixuan Zhang1, Lingdi Wang1, Fengjuan Fan1, Lu Zhu1, Zhigang Li1, Xiangbo Ruan1, Heng Huang1, Zhenzhen Wang1, Zhihua Huang2, Yuliang Huang2, Xiaoqiang Yan2, Yan Chen2
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-22RA1 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.
In this study, we demonstrate that IL-22 alleviates hepatic steatosis induced by high fat diet (HFD).
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-22RA1. 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-α in the liver was decreased by long-term rmIL-22 administration.
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.
