Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty liver
Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty liver
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DOI：
10.3748/wjg.v20.i7.1807
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发表时间：
2014-02-21
影响因子：
4.3
通讯作者：
Schultze, Frank Christian
中科院分区：
文献类型：
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作者：
Alwahsh, Salamah Mohammad;Xu, Min;Schultze, Frank Christian
目的：探讨脂质结合蛋白-2(Lipocalin-2，Lcn-2)在饮食性脂肪肝大鼠模型中的表达及其可能的作用机制(S)。方法：雄性SD大鼠分别饲喂液态Lieber-DeCarli(LDC)和LDC+70%果糖(L-HFR)4wk或8wk，诱发脂肪肝。以营养周到的动物为对照。用定量逆转录聚合酶链式反应和Western blotting检测肝组织中LCN-2等代谢和炎症介质的表达。分别采用酶联免疫吸附试验、放射免疫法和比色法测定血清LCN-2、空腹瘦素和血脂谱。免疫荧光染色检测LCN-2在肝脏中的定位。结果：低密度脂蛋白饲料和L高脂饲料饲料喂养的大鼠均表现为脂肪肝。在肝脏中，单核细胞趋化蛋白-1、α2-m、IL-8和Glut5mRNA的转录在两个时间点均显著增加(P<；0.001)，而TLR4、iNOS和肿瘤坏死因子-α的转录在第4周显著上调(P<；0.001)。与高密度脂蛋白-胆固醇相反，在L-高频辐射疗法中，全身低密度脂蛋白-2、空腹瘦素和甘油三酯水平升高(P<；0.001)。L补肾方组大鼠肝组织中Lcn-2、CD14、磷酸化MAPK、caspase-9、细胞色素c和4-羟基壬烯醛的蛋白表达增加。相反，在第8周时，肝脏线粒体生物源性蛋白PGC-1α的表达降低，属于L-HFR类。LCN-2在肝脏中的定位主要限于MPO+粒细胞。结论：果糖饮食上调了肝脏LCN-2的表达，这与氧化应激和线粒体功能障碍的指标增加有关。LCN-2可能参与了肝脏保护作用。(C)2014年白石登出版集团有限公司。版权所有。
AIM: To explore lipocalin-2 (LCN-2) expression and its possible role and mechanism(s) of production in rat models of diet-inducible fatty liver.METHODS: Fatty liver was triggered in male Sprague-Dawley rats fed either with liquid Lieber-DeCarli (LDC) or LDC + 70% cal fructose (L-HFr) diet for 4 or 8 wk. Chow-nourished animals served as controls. Hepatic expression of LCN-2 and other metabolic and inflammatory mediators was assessed by quantitative reverse transcription polymerase chain reaction and Western blotting. Serum LCN-2, fasting leptin, and lipid profile were evaluated via Enzyme-Linked Immunosorbent Assay, Radioimmunoassay, and colorimetric assays, respectively. The localization of LCN-2 in the liver was detected by using immunofluorescence staining. Furthermore, HE stain was used to evaluate hepatic fat degeneration and inflammation.RESULTS: Both LDC-fed and L-HFr-fed rat histologically featured fatty liver. In the liver, mRNA transcriptions of Mcp-1, a2-m, Il-8 and Glut5 were increased in the L-HFr group at both time points (P < 0.001), while the transcription of Tlr4, Inos, and Tnf-alpha was significantly up-regulated at week 4. Interestingly, hepatic Lcn-2 expression was 90-fold at week 4 and 507-fold at week 8 higher in L-HFr-subjected rats vs control (P < 0.001). In contrast to HDL-cholesterol, systemic levels of LCN-2, fasting leptin and triglycerides were elevated in the L-HFr regimen (P < 0.001). Moreover, protein expression of hepatic LCN-2, CD14, phospho-MAPK, caspase-9, cytochrome c and 4-hydroxynonenal was increased in the L-HFr group. Conversely, the hepatic expression of PGC-1 alpha (a mitochondrial-biogenic protein) was reduced in the L-HFr category at week 8. The localization of LCN-2 in the liver was predominantly restricted to MPO+ granulocytes.CONCLUSION: Fructose diet up-regulates hepatic LCN-2 expression, which correlates with the increased indicators of oxidative stress and mitochondrial dysfunction. The LCN-2 may be involved in liver protection. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.