Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
J Hepatol. 2013 Sep;59(3):563-70. doi: 10.1016/j.jhep.2013.04.025. Epub 2013 May 9.
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.
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.
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-1β (IL-1β), and tumor necrosis factor-α (TNFα), elevation of total nitric oxides, and increase in cd68-, cd163-, TNFα-, and/or COX-2 positive immune cells in the liver. When investigating liver cell types, LOOH elevated the secretion of TNFα, p38MAPK phosphorylation, and mRNA levels of NOS-2, COX-2, and TNFα, 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.
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.
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。导致非炎症性脂肪变性向 NASH 进展的机制在很大程度上尚不清楚。在这里，我们研究了摄入过氧化物脂质（如存在于西方饮食中的）是否会引发肝炎症。
通过灌胃给大鼠服用含有过氧化物脂肪酸的玉米油，共 6 天。在另一种方法中，从未处理的肝脏中分离出肝细胞（HC）、内皮细胞（EC）和库普弗细胞（KC），进行培养，并与过氧亚油酸（LOOH；亚油酸（LH）是玉米油中的主要脂肪酸）孵育。体内和体外研究获得的样本主要通过 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脂质过氧化增加，诱导型一氧化氮合酶-2（NOS-2）、环氧化酶-2（COX-2）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNFα）上调，总一氧化氮增加，以及肝内 CD68-、CD163-、TNFα-和/或 COX-2 阳性免疫细胞增加。当研究肝细胞类型时，LOOH 升高了 TNFα、p38MAPK 磷酸化和 NOS-2、COX-2 和 TNFα 的 mRNA 水平，主要在 KC 中。p38MAPK 抑制可阻断基因表达的升高，表明 p38MAPK 激活参与 LOOH 的促炎作用。
这些数据首次表明，摄入过氧化物脂肪酸会给身体带来相当大的促炎刺激，到达肝脏并可能引发肝炎症的发生。
