Food-derived peroxidized fatty acids may trigger hepatic inflammation: A novel hypothesis to explain steatohepatitis
Food-derived peroxidized fatty acids may trigger hepatic inflammation: A novel hypothesis to explain steatohepatitis
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DOI：
10.1016/j.jhep.2013.04.025
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发表时间：
2013-09-01
影响因子：
25.7
通讯作者：
Grasl-Kraupp, Bettina
中科院分区：
文献类型：
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作者：
Boehm, Therese;Berger, Heidi;Grasl-Kraupp, Bettina
背景与目的：肥胖和肝脂肪变性常与非酒精性脂肪性肝炎（NASH）的发生有关。驱动非炎症性脂肪变性进展为NASH的机制在很大程度上是未知的。在这里，我们调查是否摄入过氧化脂质，作为目前在西式饮食，触发肝脏inflammation.Methods的发展：玉米油含有过氧化脂肪酸被灌胃给大鼠6天。在一种单独的方法中，从未处理的肝脏中分离肝细胞（HC）、内皮细胞（EC）和枯否细胞（KC），进行培养，并与过氧化亚油酸（LOOH;亚油酸（LH）是玉米油中的主要脂肪酸）一起孵育。从体内和体外研究中获得的样品主要通过qRT-PCR和脂质过氧化产物的生化测定进行研究。用过氧化玉米油处理大鼠导致肝脏脂质过氧化增加，一氧化氮合成酶-2（NOS-2）、环氧合酶-2（考克斯-2）、白细胞介素-1 β（IL-1 β）（IL-1 β）和肿瘤坏死因子-α（TNF α），总一氧化氮的升高，以及肝脏中cd 68-、cd 163-、TNF α-和/或考克斯-2阳性免疫细胞的增加。当研究肝细胞类型时，LOOH升高TNF α的分泌、p38 MAPK磷酸化以及NOS-2、考克斯-2和TNF α的mRNA水平，主要在KC中。基因表达的升高可以通过抑制p38 MAPK，这表明，p38 MAPK的激活参与的促炎作用的LOOH.Conclusions：这些数据表明，第一次摄入过氧化脂肪酸携带相当大的促炎刺激到体内，到达肝脏，并可能引发肝脏炎症的发展。(C)2013年欧洲肝脏研究协会。由Elsevier B出版。V.保留所有权利。
Background & Aims: Obesity and hepatic steatosis are frequently associated with the development of a non-alcoholic steatohepatitis (NASH). The mechanisms driving progression of a non-inflamed steatosis to NASH are largely unknown. Here, we investigated whether ingestion of peroxidized lipids, as being present in Western style diet, triggers the development of hepatic inflammation.Methods: Corn oil containing peroxidized fatty acids was administered to rats by gavage for 6 days. In a separate approach, hepatocytes (HC), endothelial (EC) and Kupffer cells (KC) were isolated from untreated livers, cultured, and incubated with peroxidized linoleic acid (LOOH; linoleic acid (LH) being the main fatty acid in corn oil). Samples obtained from in vivo and in vitro studies were mainly investigated by qRT-PCR and biochemical determinations of lipid peroxidation products.Results: Rat treatment with peroxidized corn oil resulted in increased hepatic lipid peroxidation, upregulation of nitric oxide synthetase-2 (NOS-2), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF alpha), elevation of total nitric oxides, and increase in cd68-, cd163-, TNF alpha-, and/or COX-2 positive immune cells in the liver. When investigating liver cell types, LOOH elevated the secretion of TNF alpha, p38MAPK phosphorylation, and mRNA levels of NOS-2, COX-2, and TNF alpha, mainly in KC. The elevation of gene expression could be abrogated by inhibiting p38MAPK, which indicates that p38MAPK activation is involved in the pro-inflammatory effects of LOOH.Conclusions: These data show for the first time that ingestion of peroxidized fatty acids carries a considerable pro-inflammatory stimulus into the body which reaches the liver and may trigger the development of hepatic inflammation. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.