Toyama Tomoaki, Kudo Naomi, Mitsumoto Atsushi, Kawashima Yoichi
Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
Lipids. 2005 May;40(5):463-70. doi: 10.1007/s11745-005-1405-1.
The regulation of palmitoyl-CoA chain elongation (PCE) by clofibric acid [2-(4-chlorophenoxy)-2-methylpropionic acid] was investigated in comparison with stearoyl-CoA desaturase (SCD) in the liver of obese Zucker fa/fa rats. The proportion of oleic acid in the hepatic lipids of Zucker obese rats is 2.7 times higher than that of lean littermates. The activities of PCE and SCD in the liver of Zucker obese rats were markedly higher than in lean rats, and the hepatic uptake of 2-deoxyglucose (2-DG) was also higher in Zucker obese rats compared with lean rats. The increased activities of SCD and PCE in Zucker obese rats were due to the enhanced expression of mRNA of both SCD1 and rat FA elongase 2 (rELO2), but not SCD2 or rELO1. The proportion of oleic acid in the liver was significantly increased by the administration of clofibric acid to Zucker obese rats, and the hepatic PCE activity and rELO2 mRNA expression, but not the SCD activity or SCD1 mRNA expression, were increased in response to clofibric acid treatment. By contrast, the activities of both PCE and SCD and the mRNA expression of SCD1 and rELO2 in the liver were increased by the treatment of Zucker lean rats with clofibric acid. Multiple regression analysis, which was performed to determine the relationships involving PCE activity, SCD activity, and the proportion of oleic acid, revealed that the three parameters were significantly correlated and that the standardized partial regression coefficient of PCE was higher than that of SCD. These results indicate that oleic acid is synthesized by the concerted action of PCE and SCD and that PCE plays a crucial role in the formation of oleic acid when Zucker fa/fa rats are given clofibric acid.
在肥胖的Zucker fa/fa大鼠肝脏中，研究了氯贝酸[2-(4-氯苯氧基)-2-甲基丙酸]对棕榈酰辅酶A链延长（PCE）的调节作用，并与硬脂酰辅酶A去饱和酶（SCD）进行了比较。Zucker肥胖大鼠肝脏脂质中油酸的比例比瘦的同窝大鼠高2.7倍。Zucker肥胖大鼠肝脏中PCE和SCD的活性明显高于瘦大鼠，并且与瘦大鼠相比，Zucker肥胖大鼠肝脏对2-脱氧葡萄糖（2-DG）的摄取也更高。Zucker肥胖大鼠中SCD和PCE活性的增加是由于SCD1和大鼠脂肪酸延长酶2（rELO2）的mRNA表达增强，而不是SCD2或rELO1。给Zucker肥胖大鼠施用氯贝酸后，肝脏中油酸的比例显著增加，并且氯贝酸处理后肝脏PCE活性和rELO2 mRNA表达增加，但SCD活性或SCD1 mRNA表达未增加。相比之下，用氯贝酸处理Zucker瘦大鼠后，肝脏中PCE和SCD的活性以及SCD1和rELO2的mRNA表达均增加。进行多元回归分析以确定涉及PCE活性、SCD活性和油酸比例的关系，结果显示这三个参数显著相关，并且PCE的标准化偏回归系数高于SCD。这些结果表明，油酸是由PCE和SCD的协同作用合成的，并且当给Zucker fa/fa大鼠施用氯贝酸时，PCE在油酸的形成中起关键作用。
