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Biochem Pharmacol. 2019 Nov 28:113736. doi: 10.1016/j.bcp.2019.113736. [Epub ahead of print]

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

Author information

1
Department of Food Science, Aarhus University, Denmark.
2
Department of Biology, Copenhagen University, Denmark.
3
Department of Food Science, Aarhus University, Denmark. Electronic address: Martink.rasmussen@food.au.dk.

Abstract

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 1α (PGC-1α), 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-1α (LKO) mice of both sexes, fasted for 18 hours 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-1α 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-1α had no effect on the apparent metabolome, where fasting vs fed was the only discriminate in the following multivariate analysis. In conclusion, hepatic PGC-1α is not essential for the fasting-induced regulation of hepatic CYP's.

KEYWORDS:

Detoxification; Energy metabolism; Liver; Metabolomics, PGC-1α; Nuclear receptors

PMID:
31786263
DOI:
10.1016/j.bcp.2019.113736

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