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

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 crit...

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Main Authors: Régnier, Marion, Polizzi, Arnaud, Lippi, Yannick, Fouché, Edwin, Michel, Géraldine, Lukowicz, Céline, Smati, Sarra, Marrot, Alain, Lasserre, Frédéric, Naylies, Claire, Batut, Aurélie, Viars, Fanny, Bertrand-Michel, Justine, Postic, Catherine, Loiseau, Nicolas, Wahli, Walter, Guillou, Hervé, Montagner, Alexandra
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Journal Article
Language:English
Published: 2020
Subjects:
Online Access:https://hdl.handle.net/10356/139085
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author Régnier, Marion
Polizzi, Arnaud
Lippi, Yannick
Fouché, Edwin
Michel, Géraldine
Lukowicz, Céline
Smati, Sarra
Marrot, Alain
Lasserre, Frédéric
Naylies, Claire
Batut, Aurélie
Viars, Fanny
Bertrand-Michel, Justine
Postic, Catherine
Loiseau, Nicolas
Wahli, Walter
Guillou, Hervé
Montagner, Alexandra
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Régnier, Marion
Polizzi, Arnaud
Lippi, Yannick
Fouché, Edwin
Michel, Géraldine
Lukowicz, Céline
Smati, Sarra
Marrot, Alain
Lasserre, Frédéric
Naylies, Claire
Batut, Aurélie
Viars, Fanny
Bertrand-Michel, Justine
Postic, Catherine
Loiseau, Nicolas
Wahli, Walter
Guillou, Hervé
Montagner, Alexandra
author_sort Régnier, Marion
collection NTU
description 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.
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spelling ntu-10356/1390852020-05-15T05:49:22Z Insights into the role of hepatocyte PPARα activity in response to fasting Régnier, Marion Polizzi, Arnaud Lippi, Yannick Fouché, Edwin Michel, Géraldine Lukowicz, Céline Smati, Sarra Marrot, Alain Lasserre, Frédéric Naylies, Claire Batut, Aurélie Viars, Fanny Bertrand-Michel, Justine Postic, Catherine Loiseau, Nicolas Wahli, Walter Guillou, Hervé Montagner, Alexandra Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Nuclear Receptor PPARα 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. 2020-05-15T05:49:22Z 2020-05-15T05:49:22Z 2017 Journal Article Régnier, M., Polizzi, A., Lippi, Y., Fouché, E., Michel, G., Lukowicz, C., . . . Montagner, A. (2018). Insights into the role of hepatocyte PPARα activity in response to fasting. Molecular and Cellular Endocrinology, 471, 75-88. doi:10.1016/j.mce.2017.07.035 0303-7207 https://hdl.handle.net/10356/139085 10.1016/j.mce.2017.07.035 28774777 2-s2.0-85026660982 471 75 88 en Molecular and Cellular Endocrinology © 2017 Elsevier B.V. All rights reserved.
spellingShingle Science::Medicine
Nuclear Receptor
PPARα
Régnier, Marion
Polizzi, Arnaud
Lippi, Yannick
Fouché, Edwin
Michel, Géraldine
Lukowicz, Céline
Smati, Sarra
Marrot, Alain
Lasserre, Frédéric
Naylies, Claire
Batut, Aurélie
Viars, Fanny
Bertrand-Michel, Justine
Postic, Catherine
Loiseau, Nicolas
Wahli, Walter
Guillou, Hervé
Montagner, Alexandra
Insights into the role of hepatocyte PPARα activity in response to fasting
title Insights into the role of hepatocyte PPARα activity in response to fasting
title_full Insights into the role of hepatocyte PPARα activity in response to fasting
title_fullStr Insights into the role of hepatocyte PPARα activity in response to fasting
title_full_unstemmed Insights into the role of hepatocyte PPARα activity in response to fasting
title_short Insights into the role of hepatocyte PPARα activity in response to fasting
title_sort insights into the role of hepatocyte pparα activity in response to fasting
topic Science::Medicine
Nuclear Receptor
PPARα
url https://hdl.handle.net/10356/139085
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