Insights into the role of hepatocyte PPARα activity in response to fasting.

Details

Serval ID
serval:BIB_34C4C5B5A5DA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Insights into the role of hepatocyte PPARα activity in response to fasting.
Journal
Molecular and cellular endocrinology
Author(s)
Régnier M., Polizzi A., Lippi Y., Fouché E., Michel G., Lukowicz C., Smati S., Marrot A., Lasserre F., Naylies C., Batut A., Viars F., Bertrand-Michel J., Postic C., Loiseau N., Wahli W., Guillou H., Montagner A.
ISSN
1872-8057 (Electronic)
ISSN-L
0303-7207
Publication state
Published
Issued date
15/08/2018
Peer-reviewed
Oui
Volume
471
Pages
75-88
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The liver plays a central role in the regulation of fatty acid metabolism. Hepatocytes are highly sensitive to nutrients and hormones that drive extensive transcriptional responses. Nuclear hormone receptors are key transcription factors involved in this process. Among these factors, PPARα is a critical regulator of hepatic lipid catabolism during fasting. This study aimed to analyse the wide array of hepatic PPARα-dependent transcriptional responses during fasting. We compared gene expression in male mice with a hepatocyte specific deletion of PPARα and their wild-type littermates in the fed (ad libitum) and 24-h fasted states. Liver samples were acquired, and transcriptome and lipidome analyses were performed. Our data extended and confirmed the critical role of hepatocyte PPARα as a central for regulator of gene expression during starvation. Interestingly, we identified novel PPARα-sensitive genes, including Cxcl-10, Rab30, and Krt23. We also found that liver phospholipid remodelling was a novel fasting-sensitive pathway regulated by PPARα. These results may contribute to investigations on transcriptional control in hepatic physiology and underscore the clinical relevance of drugs that target PPARα in liver pathologies, such as non-alcoholic fatty liver disease.
Keywords
Animals, Fasting, Gene Expression Profiling, Gene Expression Regulation, Glycolipids/metabolism, Hepatocytes/metabolism, Homeostasis, Lipid Metabolism/genetics, Liver/metabolism, Mice, Inbred C57BL, PPAR alpha/metabolism, Transcriptome/genetics, FGF21, Ketone bodies, Lipolysis, NAFLD, NASH, Nuclear receptor, PPARα, Steatosis, Transcriptome
Pubmed
Web of science
Create date
05/09/2017 16:43
Last modification date
20/08/2019 13:21
Usage data