Toyama Tomoaki, Kudo Naomi, Mitsumoto Atsushi, Hibino Yasuhide, Tsuda Tadashi, Kawashima Yoichi
Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado, Saitama, Japan.
J Pharmacol Sci. 2007 Apr;103(4):383-90. doi: 10.1254/jphs.fp0061124. Epub 2007 Mar 31.
A mechanism by which fibrates control stearoyl-CoA desaturase (SCD) in the liver was studied. Treatment of rats with 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) or feeding of a fat-free diet markedly elevated hepatic activity of SCD. Both the treatment with clofibric acid and the feeding of the fat-free diet caused an increase in the steady-state level of SCD1 mRNA and enhanced transcriptional rate. The half-lives of SCD for control rats, rats treated with clofibric acid rats, and rats fed the fat-free diet were estimated to be 2.0, 3.9, and 1.9 h, respectively. Activity of palmitoyl-CoA chain elongase (PCE) was increased by both clofibric acid treatment and feeding of the fat-free diet as was observed with SCD. Steady-state level of rat fatty acid elongase 2 mRNA was increased by the treatment with clofibric acid or feeding of fat-free diet, although the transcriptional rate was not altered. Different from SCD, PCE was highly stable and its half-life was not changed by either clofibric acid or fat-free diet. These results strongly suggest that the decreased degradation of SCD is responsible for the increase in its activity in addition to increased transcription of SCD1 in the rats treated with clofibric acid.
研究了贝特类药物调控肝脏中硬脂酰辅酶A去饱和酶（SCD）的机制。用2-（4-氯苯氧基）-2-甲基丙酸（氯贝酸）处理大鼠或给予无脂饮食，均能显著提高肝脏SCD的活性。氯贝酸处理和无脂饮食喂养均导致SCD1 mRNA的稳态水平升高，并提高转录速率。对照大鼠、氯贝酸处理的大鼠和无脂饮食喂养的大鼠的SCD半衰期分别估计为2.0、3.9和1.9小时。与SCD情况类似，氯贝酸处理和无脂饮食喂养均能提高棕榈酰辅酶A链延长酶（PCE）的活性。氯贝酸处理或无脂饮食喂养可使大鼠脂肪酸延长酶2 mRNA的稳态水平升高，尽管转录速率未发生改变。与SCD不同，PCE高度稳定，其半衰期不受氯贝酸或无脂饮食的影响。这些结果有力地表明，在氯贝酸处理的大鼠中，除了SCD1转录增加外，SCD降解减少也是其活性增加的原因。
