Staprans I, Rapp J H, Pan X M, Feingold K R
Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
J Lipid Res. 1996 Feb;37(2):420-30.
Previous studies have shown that the quantity of oxidized lipids in the diet directly correlates with the level of oxidized chylomicrons in mesenteric lymph and the level of oxidized lipids in endogenous lipoproteins such as very low density lipoprotein (VLDL) and low density lipoprotein (LDL). The aim of the present study was to determine whether oxidized fatty acids in the diet are delivered via chylomicrons to the liver and whether these lipids are repackaged and secreted in VLDL. In these experiments, oxidized [14C]linoleic acid was utilized as a marker for oxidized dietary fats. When we determined the metabolism of nonoxidized and oxidized [14C]linoleic acid-labeled chylomicrons, we found that hepatic uptake was similar with 13.57 +/- 0.84% of nonoxidized and 13.40 +/- 0.96% of oxidized linoleic acid delivered to the liver 30 min after chylomicron administration. Additionally, uptake by the extrahepatic tissues was also similar. When the hepatic secretion of VLDL was determined in an in vitro perfusion system after the administration of nonoxidized and oxidized linoleic acid-labeled chylomicrons to intact animals, we found that oxidized linoleic acid was utilized for the formation and secretion of VLDL. After the administration of labeled nonoxidized and oxidized linoleic acid, 0.86 +/- 0.07% and 0.70 +/- 0.09% of the administered label was found in the liver perfusate at 2 h, respectively. The presence of oxidized linoleic acid in oxidized VLDL was confirmed by demonstrating the presence of hydroperoxide-derived hydroxy octadecanoic acid. Thus, our findings demonstrate that oxidized dietary lipids are delivered to the liver via chylomicrons where they are utilized for synthesis of endogenous lipoproteins such as VLDL.
先前的研究表明，饮食中氧化脂质的量与肠系膜淋巴中氧化乳糜微粒的水平以及内源性脂蛋白（如极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL））中氧化脂质的水平直接相关。本研究的目的是确定饮食中的氧化脂肪酸是否通过乳糜微粒输送到肝脏，以及这些脂质是否被重新包装并以VLDL的形式分泌。在这些实验中，氧化的[14C]亚油酸被用作氧化膳食脂肪的标志物。当我们测定未氧化和氧化的[14C]亚油酸标记的乳糜微粒的代谢时，我们发现乳糜微粒给药30分钟后，肝脏摄取相似，未氧化亚油酸的摄取量为13.57±0.84%，氧化亚油酸的摄取量为13.40±0.96%。此外，肝外组织的摄取也相似。当在完整动物中给予未氧化和氧化的亚油酸标记的乳糜微粒后，在体外灌注系统中测定VLDL的肝脏分泌时，我们发现氧化亚油酸被用于VLDL的形成和分泌。给予标记的未氧化和氧化亚油酸后，在2小时时肝脏灌注液中分别发现给药标记物的0.86±0.07%和0.70±0.09%。通过证明过氧化氢衍生的羟基十八烷酸的存在，证实了氧化VLDL中存在氧化亚油酸。因此，我们的研究结果表明，氧化的膳食脂质通过乳糜微粒输送到肝脏，在那里它们被用于合成内源性脂蛋白，如VLDL。
