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Hepatic PGC-1 alpha is not essential for fasting-induced cytochrome p450 regulation in mouse liver

机译:肝PGC-1α不是必不可少的小鼠肝脏中诱导的细胞色素p450调节

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Fasting has been shown to regulate the expression of the cytochrome p450 (CYP) enzyme system in the liver. However, the exact mechanism behind the fasting-induced regulation of the CYP's remains unknown. In the present study we tested the hypothesis that the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha), which is a key-regulator of energy metabolism, is responsible for the fasting-induced regulation of the CYP's. Lox/lox and liver specific PGC-1 alpha (LKO) mice of both sexes, fasted for 18 h and the content of the CYP's as well as the hepatic metabolome was assessed. Fasting increased the mRNA content of Cyp2a4, Cyp2e1, Cyp3a11 and Cyp4a10. The fasting-induced response in Cyp4a10 mRNA content was different between lox/lox and LKO mice, while the absence of PGC-1 alpha had no effect on the fasting-induced response for the other Cyp's. Moreover, the fasting-induced response in mRNA content of Sirtinus 1 and Perilipin 2 was different between lox/lox and LKO mice. Only the CYP1A isoform showed a fasting-induced response at the protein level. Absence of hepatic PGC-1 alpha had no effect on the apparent metabolome, where fasting vs fed was the only discriminate in the following multivariate analysis. In conclusion, hepatic PGC-1 alpha is not essential for the fasting-induced regulation of hepatic CYP's.
机译:已经证明禁食来调节肝脏中细胞色素P450(CYP)酶系统的表达。然而,CYP的禁食调节背后的确切机制仍然是未知的。在本研究中,我们测试了过氧化物酶体增殖物激活的受体γ1α(PGC-1α)的假设,这是能量代谢的关键调节器,负责CYP的禁食诱导调节。洛克斯/ LOX和肝脏特异性PGC-1α(LKO)小鼠的两性,禁食18小时和CYP的含量以及肝脏代谢物。禁食增加CYP2A4,CYP2E1,CYP3A11和CYP4A10的mRNA含量。 CYP4A10 mRNA含量的禁食诱导的响应在LOX / LOX和LKO小鼠之间是不同的,而PGC-1α的不存在对其他CYP的禁食响应没有影响。此外,Sirtinus 1和Perilipin 2的mRNA含量中的禁食响应在LOx / LOX和LKO小鼠之间是不同的。只有CYP1A同种型显示蛋白质水平的禁食响应。没有肝脏PGC-1α对表观代谢物没有影响,其中馈电饲料的禁食Vs是唯一的多变量分析中的唯一区分。总之,肝PGC-1α不是必不可少的肝CYP的禁食调控。

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