Toyama Tomoaki, Kudo Naomi, Hibino Yasuhide, Mitsumoto Atsushi, Nishikawa Masazumi, Kawashima Yoichi
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
J Pharmacol Sci. 2007 Jun;104(2):137-45. doi: 10.1254/jphs.fp0060997. Epub 2007 May 31.
The effects of a peroxisome proliferator activated receptor gamma (PPARgamma) agonist on hepatic stearoyl-CoA desaturase (SCD) in insulin-resistant and obese Zucker fa/fa rats were studied. The administration of pioglitazone, a PPARgamma agonist, to Zucker obese rats greatly improved their insulin sensitivity. The treatment of Zucker obese rats with pioglitazone did not affect the index of fatty acid desaturation of either serum or liver. Hepatic SCD activity and the mRNA level of SCD1 were not changed by treatment of the rats with pioglitazone. The activity of palmitoly-CoA chain elongase, which is involved in the biosynthesis of oleic acid in concert with SCD, was not significantly altered when Zucker obese rats received pioglitazone. Although neither the activity nor mRNA expression of acyl-CoA oxidase was changed by treatment of Zucker obese rats with pioglitazone, the mRNA expressions of both sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase sensitively responded to the challenge by pioglitazone. These results suggest that the insulin sensitivity of insulin-resistant and obese Zucker fa/fa rats is improved by pioglitazone independently of SCD activity.
研究了过氧化物酶体增殖物激活受体γ（PPARγ）激动剂对胰岛素抵抗和肥胖的Zucker fa/fa大鼠肝脏硬脂酰辅酶A去饱和酶（SCD）的影响。给Zucker肥胖大鼠施用PPARγ激动剂吡格列酮可显著改善其胰岛素敏感性。用吡格列酮治疗Zucker肥胖大鼠对血清或肝脏的脂肪酸去饱和指数没有影响。用吡格列酮治疗大鼠后，肝脏SCD活性和SCD1的mRNA水平没有改变。当Zucker肥胖大鼠接受吡格列酮时，与SCD协同参与油酸生物合成的棕榈酰辅酶A链延长酶的活性没有显著改变。虽然用吡格列酮治疗Zucker肥胖大鼠后酰基辅酶A氧化酶的活性和mRNA表达均未改变，但固醇调节元件结合蛋白-1c和乙酰辅酶A羧化酶的mRNA表达对吡格列酮的刺激敏感。这些结果表明，吡格列酮可独立于SCD活性改善胰岛素抵抗和肥胖的Zucker fa/fa大鼠的胰岛素敏感性。
