Studies on the regulation of fatty acid biosynthesis by drugs

药物调控脂肪酸生物合成的研究

• 批准号: 12671125
• 负责人: KAWASHIMA Yoichi
• 金额: $ 2.05万
• 依托单位: Josai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671125/
• 关键词: △9 desaturase; clofibric acid; palmitoyl-CoA chain elongase; insulin; dehydroepiandrosterone; fatty acid; 脂肪酸酸化; VLDL分泌; 糖尿病; PPAR

Effects of clofibric acid and dehydroepiandrosterone (DHEA) on the formation of oleic acid was studied in combination with diabetes or carbohydrate administration. Both clofibric acid and DHEA caused an increase in oleic acid and a decrease in linoleic acid and docosahexaenoic acid. By contrast, the proportion of oleic acid and palmitoleic acid was increased while the proportion of linoleic acid and arachidonic acid decreased upon carbohydrate administration. The activities of △9 desaturase (SCD) and palmitoyl-CoA chain elongase (PCE) were increased by DHEA, carbohydrate and clofibric acid. The induction of both enzymes were different when clofibric acid was treated in combination with carbohydrate. The proportion of oleic acid was increased at the same condition. In diabetic state, both SCD and PCE activities while glucose did not. DHEA accelerated fatty acid oxidation in mitochondria despite that DHEA induced the enzymes responsible for fatty acid oxidation in both mitochondria and peroxisomes in vitro.The above results suggest that SCD and PCE were induced by various conditions, however, fatty acid composition differed between the conditions. Different induction and consumption of fatty acid may be responsible for different effects on fatty acid composition.

结合糖尿病或碳水化合物给药，研究了氯贝酸和脱氢表雄酮 (DHEA) 对油酸形成的影响。氯贝酸和DHEA均导致油酸增加以及亚油酸和二十二碳六烯酸减少。相比之下，给予碳水化合物后，油酸和棕榈油酸的比例增加，而亚油酸和花生四烯酸的比例减少。 DHEA、碳水化合物和氯贝酸可提高△9去饱和酶（SCD）和棕榈酰辅酶A链延长酶（PCE）的活性。当氯贝酸与碳水化合物联合处理时，两种酶的诱导是不同的。在相同条件下增加油酸的比例。在糖尿病状态下，SCD 和 PCE 均具有活性，而葡萄糖则不具有活性。尽管DHEA在体外诱导了线粒体和过氧化物酶体中负责脂肪酸氧化的酶，但DHEA加速了线粒体中的脂肪酸氧化。上述结果表明SCD和PCE是由各种条件诱导的，然而，不同条件下的脂肪酸组成不同。脂肪酸的不同诱导和消耗可能对脂肪酸组成产生不同的影响。

项目成果

Imai, K.: "Effects of dehydroepiandrosterone on oleic acid formation in the liver of rats, mice and guinea pigs"Jpn.J.Pharmacol.. 86. 437-447 (2001)

Imai, K.：“脱氢表雄酮对大鼠、小鼠和豚鼠肝脏中油酸形成的影响”Jpn.J.Pharmacol.. 86. 437-447 (2001)

Mizuguchi, H., Kudo, N. and Kawashima, Y.: "Metabolic alterations by clofibric acid in the formation of molecular species of phosphatidylcholine in the liver of rats"Biochem. Pharmacol.. 62. 853-861 (2001)

Mizuguchi, H.、Kudo, N. 和 Kawashima, Y.：“氯贝酸对大鼠肝脏中磷脂酰胆碱分子种类形成的代谢改变”Biochem。

Mizuguchi,H, et al.: "Metabolic alterations by clofibric acid in the formation of molecular species of phosphatidylcholine in the liver of rats"Biochemical Pharmacology. (in press). (2001)

Mizuguchi, H 等人：“氯贝酸对大鼠肝脏中磷脂酰胆碱分子种类形成的代谢改变”生化药理学。

Kudo, N., Toyama, T., Mitsumoto, A. and Kawashima, Y.: "Regulation by carbohydrate and clofibiric acid of palmitoyl-CoA chain elongation in the liver of rats"Lipids, in press.

Kudo, N.、Toyama, T.、Mitsumoto, A. 和 Kawashima, Y.：“碳水化合物和氯贝伯酸对大鼠肝脏中棕榈酰辅酶 A 链伸长的调节”脂质，正在出版。

Imai, K., Kudo, N., Koyama, M., Shirahata, A. and Kawashima, Y.: "Effects of dehydroepiandrosterone on oleic acid information in the liver of rats, mice and guinea pigs"Jpn. J. Pharmacol.. 86. 437-447 (2001)

Imai, K.、Kudo, N.、Koyama, M.、Shirahata, A. 和 Kawashima, Y.：“脱氢表雄酮对大鼠、小鼠和豚鼠肝脏中油酸信息的影响”Jpn。