Chiu Cheng-Ying, Smyl Christopher, Dogan Inci, Rothe Michael, Weylandt Karsten-H
Department of Medicine, Division of Hepatology and Gastroenterology, Charité University Medicine Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
Lipid Clinic, Experimental and Clinical Research Centre (ECRC), Charité University Medicine and Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany.
Biology (Basel). 2017 Feb 4;6(1):9. doi: 10.3390/biology6010009.
Polyunsaturated fatty acids (PUFA) are precursors of bioactive metabolites and mediators. In this study, the profile of hydroxyeicosatetraenoic (HETE), hydroxyeicosapentaenoic (HEPE) and hydroxydocosahexaenoic (HDHA) acids derived from arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in colon, liver, lung, spleen, muscle, heart and kidney tissue of healthy wildtype mice were characterized, and compared to profiles in organs from transgenic fat-1 mice engineered to express the fat-1 gene encoding an n-3 desaturase and thereby with endogenously elevated n-3 PUFA levels. PUFAs were measured using gas chromatography. The lipid metabolites were assayed using LC-MS/MS. AA and DHA were the prominent PUFAs in wildtype and fat-1 mice. EPA levels were low in both groups even though there was a significant increase in fat-1 organs with an up to 12-fold increase in fat-1 spleen and kidney. DHA levels increased by approximately 1.5-fold in fat-1 as compared to wildtype mice. While HETEs remained the same or decreased moderately and HDHAs increased 1- to 3-fold, HEPE formation in fat-1 tissues increased from 8- (muscle) to 44-fold (spleen). These findings indicate distinct profiles of monohydroxy lipid metabolites in different organs and strong utilization of EPA for HEPE formation, by which moderate EPA supplementation might trigger formation of biologically active EPA-derived resolvins.
多不饱和脂肪酸（PUFA）是生物活性代谢物和介质的前体。在本研究中，对健康野生型小鼠的结肠、肝脏、肺、脾脏、肌肉、心脏和肾脏组织中源自花生四烯酸（AA）、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）的羟基二十碳四烯酸（HETE）、羟基二十碳五烯酸（HEPE）和羟基二十二碳六烯酸（HDHA）的情况进行了表征，并与转基因fat-1小鼠器官中的情况进行了比较，这些小鼠经过基因工程改造以表达编码n-3去饱和酶的fat-1基因，从而内源性地提高了n-3多不饱和脂肪酸水平。使用气相色谱法测量多不饱和脂肪酸。使用液相色谱-串联质谱法测定脂质代谢物。AA和DHA是野生型和fat-1小鼠中的主要多不饱和脂肪酸。两组中的EPA水平都很低，尽管fat-1小鼠的器官中有显著增加，fat-1小鼠的脾脏和肾脏中增加了多达12倍。与野生型小鼠相比，fat-1小鼠中的DHA水平增加了约1.5倍。虽然HETE保持不变或略有下降，HDHA增加了1至3倍，但fat-1组织中HEPE的形成从8倍（肌肉）增加到44倍（脾脏）。这些发现表明不同器官中一羟基脂质代谢物的情况不同，且EPA在HEPE形成中得到大量利用，通过这种方式，适度补充EPA可能会触发具有生物活性的源自EPA的消退素的形成。
