Increased formation of polyunsaturated fatty acids and the physiological significance

多不饱和脂肪酸的形成增加及其生理意义

• 批准号: 02670993
• 负责人: KAWASHIMA Yoichi
• 金额: $ 1.54万
• 依托单位: Toyama Medical and Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670993/
• 关键词: Hypolipidemic drug; Clofibric acid; Polyunsaturated fatty acid; Molecular species; Liver; Metabolism; Phosphatidylcholine; Phosphatidylethanolamine; 生合成; クロフィブラ-ト; 脂肪酸不飽和化酵素; リン脂質アシル基組成; ω6系列脂肪酸; ペルオキシゾ-ム増殖剤

Administration of clofibric acid, a hypolipidemic drug, to rodents is known to cause proliferation of peroxisomes and hepatomegaly. The drug stimulates, to a lesser extent, proliferation of mitochondria and endolpasmic reticulum as well. Although these responses of liver to the drug are supposed to require a large amounts of phospholipids as the constituents of biogenic membranes, little information is available about the mechanism by which hepatocytes increase the supply of phospholipids for the biogenesis of membranes. The present work investigated the mechanism and obtained the following results. (1) Clofibric acid induced hepatic fatty-acid desaturases so that the formations of oleic acid and arachidonic acid were increased. (2) Upon the treatment with this drug, hepatic concentrations of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were increased. The increase in hepatic concentration of PC was caused by enhancing the activity of synthesis de novo of PC, and the conc … More entration of PE was increased by reducing the rate of turnover, but not by increasing the activity of synthesis de novo. (3) Oleic acid formed was mainly channeled to formation of palmitoyl-oleoyl species of PC, and arachidonic acid formed was preferentially utilized for formation of palmitoyl-arachidonoyl and stearoyl-arachidonoyl species of PE. (4) The administration of clofibric acid decreased a proportion of stearoyl- arachidonoyl species in PC, and the decrease caused the reduction in the level of serum arachidonic acid. Since kidney little produced arachidonic acid, the reduction in serum arachidonic acid decreased the proportion of arachidonic acid in renal PC so that formation of prostaglandin E_2 was lowered. These results suggest that hepatocytes increase the supply of phospholipids by inducing enzymes and by reducing turnover to maintain proliferating biogenic membranes with appropriate fluidity and that the changes induced in liver resulted in the reduction of prostaglandin in kidney. Less

已知对啮齿类动物给予降血脂药物氯贝酸会导致过氧化物酶体增殖和肝肿大。该药物刺激，在较小程度上，增殖的线粒体和endolpasmic网以及。虽然肝脏对药物的这些反应被认为需要大量的磷脂作为生物膜的成分，但关于肝细胞增加磷脂供应用于膜生物发生的机制的信息很少。本工作探讨了这一机制，并获得了以下结果。(1)氯贝酸诱导肝脂肪酸去饱和酶，使油酸和花生四烯酸的形成增加。(2)在用该药物治疗后，肝磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）的浓度增加。肝内PC浓度的升高是由于PC从头合成活性增强所致，而肝内PC浓度的升高则是由于肝内PC浓度的增加所致。 ...更多信息 通过降低周转率来增加PE的摄入量，而不是通过增加从头合成的活性来增加PE的摄入量。(3)形成的油酸主要用于形成PC的棕榈酰基-油酰基物种，并且形成的花生四烯酸优先用于形成PE的棕榈酰基-花生四烯酸和硬脂酰基-花生四烯酸物种。(4)氯贝酸的给药降低了PC中硬脂酰-花生四烯酸种类的比例，并且该降低引起血清花生四烯酸水平的降低。由于肾脏不产生花生四烯酸，血清花生四烯酸的降低降低了花生四烯酸在肾PC中的比例，从而降低了前列腺素E_2的形成。这些结果表明，肝细胞通过诱导酶和减少周转来增加磷脂的供应，以维持增殖的生物膜具有适当的流动性，并且肝脏中诱导的变化导致肾脏中前列腺素的减少。少

项目成果

Yoichi Kawashima: "Reduction by clofibric acid of serum arachidonic acidin rats;Effects on the acyl composition of reral phospholipids" Biochemical Pharmacology. 43. 2321-2326 (1992)

Yoichi Kawashima：“氯贝酸降低大鼠血清花生四烯酸；对现实磷脂酰基组成的影响”生化药理学。

Yoichi Kawashima: "Reduction by clofibric acid of serum arachidonic acid in rats; Effects on the acyl composition of renal phospholipids" Biochemical Pharmacology. 43. 2321-2326 (1992)

Yoichi Kawashima：“氯贝酸降低大鼠血清花生四烯酸；对肾磷脂酰基组成的影响”生化药理学。