Dietary induction of acyl chain desaturases alters the lipid composition and fluidity of rat hepatocyte plasma membranes.
Dietary induction of acyl chain desaturases alters the lipid composition and fluidity of rat hepatocyte plasma membranes.
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膳食诱导酰基链去饱和酶改变大鼠肝细胞质膜的脂质组成和流动性。
DOI：
10.1021/bi00301a021
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发表时间：
1984
期刊：
影响因子：
2.9
通讯作者：
Schachter,D
中科院分区：
文献类型：
--
作者：
Storch,J;Schachter,D
Judith Storch* 和大卫Schachter* 摘要：大鼠维持间歇性饥饿方案，然后重新喂食无脂肪饮食，以诱导肝酰基去饱和酶活性和其他参与脂质合成的酶。饮食方案对脂质组成和离体肝细胞质膜流动性的影响进行了比较，相应的影响微粒体制剂。结果表明，高脂饮食可增加质膜单烯和多烯酰基链的含量，降低膜胆固醇/磷脂摩尔比。相应地，质膜的脂质流动性显著增加，如通过1，6-二苯基-1，3，5-己三烯和12-（9-蒽氧基）硬脂酸酯的荧光偏振和1，3-二（1-芘基）丙烷的分子内受激准分子荧光所评估的。在微粒体膜中，单烯酸酰基链含量的显著增加被多烯酸含量的减少所抵消，并且没有观察到胆固醇/磷脂比的变化。相应地，微粒体膜的脂质流动性几乎保持不变。肝细胞质膜中的脂质流动性的增强伴随着（Na++ K+）依赖性腺苷三磷酸酶的比活性增加约68%。结果表明，饮食方案可以在体内调节肝细胞质膜的脂质组成、流动性和酶功能。有相当多的证据表明，肝细胞质膜的运动自由或“脂质流动性”1影响细胞器的重要活性和功能，包括（Na++ K+）-依赖性腺苷三磷酸酶[（Na++ K+）-ATP酶] 2（Keeffe等，1979）、腺苷酸环化酶（Houslay等人，1976 a，B; Dipple和Houslay，1978），以及胆汁分泌过程（Davis等，1978; Keeffe等人，1979; Simon等人，1980; Storch & Schachter，1983）。然而，调节膜流动性的机制是相对不确定的，目前的调查进行了探索的假设，肝酰基链去饱和酶的活性可以调节在体内的质膜脂质的组成和流动性。这种可能性似乎是合理的，因为β-磷脂酰基的顺式不饱和增加了单层中的分子堆积面积（Demel等人，1967; Jain，1972）和双层中的流动性（Lentz等人，1976; Seelig和Seelig，1977; King和Spector，1978; Pessin等人，1978; Klausner等人，1980年）。此外，最近的证据支持更普遍的假设，即质膜流动性可以在体内通过调节特定膜脂质的生物合成来调节。在大鼠肠上皮细胞中，胆固醇生物合成的变化调节胆固醇含量和管腔微绒毛膜的流动性（Brasitus & Schachter，1982）。本文中描述的实验利用间歇性饥饿的饮食方案，然后再喂食无脂肪饮食以诱导肝脏脂肪酰基去饱和酶活性（Oshino & Sato，1972; Strittmatter et al.，1974; Pugh & Kates，1977）。这些酶活性存在于肝匀浆的微粒体部分中，并且它们使用棕榈酸（16：0）和硬脂酸（18：0）的辅酶A硫代酯作为底物（Marsh & James，1962;霍洛威等人，1963;以诺等人，1976; Jeffcoat & James，1977）或磷脂的酰基
Judith Storch* and David Schachter* abstract: Rats were maintained on a regimen of intermittent starvation followed by refeeding a fat-free diet in order to induce hepatic acyl desaturase activities and other enzymes involved in lipid synthesis. The effects of the dietary regimen on the lipid composition and fluidity of isolated hepatocyte plasma membranes were compared to corresponding effects on microsomal preparations. The dietary regimen increased the content of monoenoic and polyenoic acyl chains and de-creased the cholesterol/phospholipid molar ratio in the plasma membranes. Accordingly, the lipid fluidity of the plasma membranes was significantly increased as assessed by the fluorescence polarization of 1, 6-diphenyl-1, 3, 5-hexatriene and 12-(9-anthroyloxy) stearate and the intramolecular excimer fluorescence of 1, 3-di (1-pyrenyl) propane. In the microsomal membranes, substantial increases in the content of monoenoic acyl chains were offset bydecreases in polyenoic acids, and no change incholesterol/phospholipid ratio was observed. Correspondingly, the lipid fluidity of the microsomal mem-branes remained almost unchanged. The enhancement of lipid fluidity in the hepatocyte plasma membranes was accompanied by an increase of approximately 68% in the specific activity of the (Na++ K+)-dependent adenosinetriphosphatase. The results demonstrate that a dietary regimen can modulate in vivo the lipid composition, fluidity, and enzyme function of the hepatocyte plasma membrane. ere is considerable evidence that the motional freedom or “lipid fluidity” 1 of the hepatocyte plasma membrane influences important activities and functions of the organelle, including the (Na++ K+)-dependent adenosinetriphosphatase [(Na++ K+)-ATPase] 2 (Keeffe et al., 1979), the adenylate cyclase (Houslay et al., 1976a, b; Dipple & Houslay, 1978), and the process of biliary secretion (Davis et al., 1978; Keeffe et al., 1979; Simon et al., 1980; Storch & Schachter, 1983). The mechanisms which regulate the membrane fluidity, however, are relatively undefined, and the present investigation was undertaken to explore the hypothesis that the activity of hepatic acyl chain desaturases can modulate in vivo the composition and fluidity of the plasma membrane lipids. This possibility seemed reasonable, inasmuch as cis unsaturation of phos-pholipid acyl groupsincreases themolecular packing area in monolayers (Demel et al., 1967; Jain, 1972) and the fluidity in bilayers (Lentz et al., 1976; Seelig & Seelig, 1977; King & Spector, 1978; Pessin et al., 1978; Klausner et al., 1980). Moreover, recent evidence supports the more general hypothesis that plasma membrane fluidity can be regulated in vivo by modulating the biosynthesis of specific membrane lipids. In rat enterocytes, changes in cholesterol biosynthesis modulate the cholesterol content and the fluidity of the luminal, microvillus membranes (Brasitus & Schachter, 1982). The experiments described in this paper utilized a dietary regimen of intermittent starvation followed by refeeding a fat-free diet to induceliver fatty acyl desaturase activities (Oshino & Sato, 1972; Strittmatter et al., 1974; Pugh & Kates, 1977). These enzyme activities are in the microsomal fractions of liver homgenates, and they use as substrates the coenzyme A thio esters of palmitic (16: 0) and stearic (18: 0) acids (Marsh & James, 1962; Holloway et al., 1963; Enoch et al., 1976; Jeffcoat & James, 1977) or the acyl groups of phospholipids