Effect of ethanol on polyunsaturated fatty acid biosynthesis in hepatocytes from spontaneously hypertensive rats.
Effect of ethanol on polyunsaturated fatty acid biosynthesis in hepatocytes from spontaneously hypertensive rats.
复制标题
乙醇对自发性高血压大鼠肝细胞多不饱和脂肪酸生物合成的影响。
DOI：
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
S. Bellenger
中科院分区：
文献类型：
--
作者：
M. Narce;J. Poisson;J. Bellenger;S. Bellenger
背景
多不饱和脂肪酸(PUFA)在酒精中毒时被修饰的膜结构中起主要作用。多不饱和脂肪酸也是参与调节血压的第二信使--二十烷基类化合物的前体。酒精与高血压和肝脏多不饱和脂肪酸代谢的改变有关。我们研究了乙醇对Wistar京都(WKY)大鼠和自发性高血压大鼠(SHR)肝细胞多不饱和脂肪酸生物合成的影响。还研究了富含n-3多不饱和脂肪酸的饮食对高血压的影响。
方法
取血压正常的雄性Wistar京都大鼠(WKY)和自发性高血压大鼠(SHR)的肝细胞，在含有不同浓度乙醇的培养液中与标记的亚油酸和DGLA孵育60min。SHR的肝细胞在饲料中添加n-3多不饱和脂肪酸，与相同的前体细胞孵育。
结果
首先，多不饱和脂肪酸的肝脏生物发生依赖于孵育液中乙醇的水平。第二，Delta5去饱和酶比Delta6去饱和酶对酒精浓度的变化更敏感。第三，在自发性高血压大鼠，在酒精中毒的肝细胞中花生四烯酸的生物合成显著减少；当乙醇浓度较高时，这种作用加强，主要是Delta5去饱和酶。第四，在乙醇存在下，饲料中添加n-3PUFA的自发性高血压大鼠肝细胞中多不饱和脂肪酸的生物发生发生了改变，特别是通过抑制Delta5的去饱和作用。
结论
我们的研究表明，肝细胞多不饱和脂肪酸的生物合成依赖于乙醇浓度。乙醇强烈抑制自发性高血压大鼠肝细胞多不饱和脂肪酸的合成，这可以解释与酒精中毒相关的心血管疾病中前列腺素前体的缺失。添加N-3多不饱和脂肪酸的饲料加强了花生四烯酸合成的抑制，这可能是通过底物竞争Delta5去饱和来实现的。这种体外方法提供了一个更好的理解酒精对与高血压有关的脂肪酸代谢的影响。
BACKGROUND
Polyunsaturated fatty acids (PUFA) play a major role in membrane structures that are modified during alcoholism. PUFA are also precursors of second messengers-eicosanoids-involved in the regulation of blood pressure. Alcohol has been related to hypertension and to alterations in liver PUFA metabolism. We investigated the effects of ethanol on PUFA biogenesis in hepatocytes of Wistar Kyoto (WKY) rats and Spontaneously Hypertensive Rats (SHR). The effects of a diet enriched with n-3 PUFA, which is known to modulate hypertension, were also studied.
METHODS
Isolated hepatocytes from male normotensive Wistar Kyoto (WKY) rats and SHR were incubated for 60 min in the presence of labeled linoleic acid and DGLA, which are precursors of the limiting desaturation steps of PUFA biosynthesis, into a medium containing different concentrations of ethanol. Hepatocytes from SHR that were fed a diet supplemented with n-3 PUFA were incubated with the same precursors.
RESULTS
First, the hepatic biogenesis of PUFA is dependent on the level of ethanol in the incubation medium. Second, Delta5 desaturase was more sensitive than Delta6 desaturase to changes in alcohol concentration. Third, in SHR, a tremendous decrease of arachidonic acid biosynthesis was evidenced in alcohol-intoxicated hepatocytes; the effect was reinforced when ethanol concentration was high, mainly for Delta5 desaturase. Fourth, in the presence of ethanol, the biogenesis of PUFA was altered in isolated hepatocytes from SHR that were fed the diet supplemented with n-3 PUFA, particularly via an inhibition of Delta5 desaturation.
CONCLUSIONS
Our study showed that hepatocyte PUFA biogenesis is dependent on ethanol concentration. Ethanol strongly inhibits the synthesis of PUFA in hepatocytes from SHR, which can explain the deficit of prostaglandin precursors observed in cardiovascular diseases linked to ethanol intoxication. n-3 PUFA supplemented diet reinforces the inhibition of arachidonic acid synthesis, likely by a substrate competition toward Delta5 desaturation. This in vitro approach provides a better understanding of the effects of ethanol on fatty acid metabolism in relation to hypertension.
DOI：
10.1016/s0021-9258(18)54882-1
发表时间：
1991-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Voss;M. Reinhart;S. Sankarappa;H. Sprecher
通讯作者：
A. Voss;M. Reinhart;S. Sankarappa;H. Sprecher
膳食脂肪酸和酒精：对细胞膜的影响。
DOI：
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发表时间：
1993
期刊：
Alcohol and alcoholism (Oxford, Oxfordshire)
影响因子：
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作者：
Reitz,RC
通讯作者：
Reitz,RC