肝臟研究領(lǐng)域的國(guó)際權(quán)威雜志Journal of Hepatology近日發(fā)表了中科院上海生科院營(yíng)養(yǎng)科學(xué)研究所陳雁研究組的最新研究成果,。陳雁研究員指導(dǎo)的博士研究生楊玲等揭示了在高脂飲食誘導(dǎo)的脂肪肝動(dòng)物模型中,，白介素-22（IL-22）通過(guò)抑制脂肪生成和炎癥相關(guān)基因的表達(dá)對(duì)脂肪肝起保護(hù)作用,。
IL-22是白介素-10家族的成員,，除了在Th17細(xì)胞中高表達(dá)之外,，在NK和NKT等細(xì)胞中也有表達(dá),。以前的研究提示了IL-22在組織損傷修復(fù)以及牛皮癬,、肝炎,、肺炎、腸炎等慢性炎癥中發(fā)揮重要作用,。IL-22的特異性受體表達(dá)在免疫系統(tǒng)以外的多種組織,。楊玲等的研究首次揭示了IL-22在肝臟脂代謝中的作用,。重組的小鼠IL-22蛋白可以快速降低肝臟中脂肪生成相關(guān)基因的表達(dá)。高脂飲食的C57BL/6小鼠和ob/ob小鼠經(jīng)過(guò)IL-22蛋白的注射,，肝臟中的甘油三酯和膽固醇水平顯著下降,，同時(shí)血清轉(zhuǎn)氨酶水平也相應(yīng)下降。另外肝臟中的TNF-alpha的表達(dá)水平也有所降低,。這些結(jié)果表明IL-22對(duì)肝臟脂肪變性具有保護(hù)作用,，并且該保護(hù)作用部分是通過(guò)下調(diào)脂肪生成相關(guān)基因和炎癥因子TNF-alpha表達(dá)實(shí)現(xiàn)的。
炎癥反應(yīng)與代謝調(diào)控有著共同的信號(hào)通路,，越來(lái)越多的炎癥相關(guān)基因被發(fā)現(xiàn)參與代謝綜合癥的致病過(guò)程,。該研究提示IL-22是繼IL-6和IL-10之后又一個(gè)參與炎癥反應(yīng)和代謝調(diào)控的細(xì)胞因子，IL-22有可能成為干預(yù)脂肪肝發(fā)生發(fā)展的新手段,。(生物谷Bioon.com)
生物谷推薦原文出處：
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.
