Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.

<h4>Background</h4>Studies in mice have shown that PPARalpha is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARalpha in human liver. Here we set out to compare the function of PPARalpha in mouse...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Maryam Rakhshandehroo, Guido Hooiveld, Michael Müller, Sander Kersten
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dc388ba769634e7492dbb1ea64b79ce8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:dc388ba769634e7492dbb1ea64b79ce8
record_format	dspace
spelling	oai:doaj.org-article:dc388ba769634e7492dbb1ea64b79ce82021-11-25T06:20:45ZComparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.1932-620310.1371/journal.pone.0006796https://doaj.org/article/dc388ba769634e7492dbb1ea64b79ce82009-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19710929/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Studies in mice have shown that PPARalpha is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARalpha in human liver. Here we set out to compare the function of PPARalpha in mouse and human hepatocytes via analysis of target gene regulation.<h4>Methodology/principal findings</h4>Primary hepatocytes from 6 human and 6 mouse donors were treated with PPARalpha agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPARalpha expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPARalpha in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPARalpha targets, including CPT1A, HMGCS2, FABP1, ACSL1, and ADFP. Several genes were identified that were specifically induced by PPARalpha in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPARalpha targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8.<h4>Conclusions/significance</h4>Our results suggest that PPARalpha activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPARalpha as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPARalpha regulates a mostly divergent set of genes in mouse and human hepatocytes.Maryam RakhshandehrooGuido HooiveldMichael MüllerSander KerstenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 8, p e6796 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maryam Rakhshandehroo Guido Hooiveld Michael Müller Sander Kersten Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
description	<h4>Background</h4>Studies in mice have shown that PPARalpha is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARalpha in human liver. Here we set out to compare the function of PPARalpha in mouse and human hepatocytes via analysis of target gene regulation.<h4>Methodology/principal findings</h4>Primary hepatocytes from 6 human and 6 mouse donors were treated with PPARalpha agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPARalpha expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPARalpha in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPARalpha targets, including CPT1A, HMGCS2, FABP1, ACSL1, and ADFP. Several genes were identified that were specifically induced by PPARalpha in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPARalpha targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8.<h4>Conclusions/significance</h4>Our results suggest that PPARalpha activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPARalpha as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPARalpha regulates a mostly divergent set of genes in mouse and human hepatocytes.
format	article
author	Maryam Rakhshandehroo Guido Hooiveld Michael Müller Sander Kersten
author_facet	Maryam Rakhshandehroo Guido Hooiveld Michael Müller Sander Kersten
author_sort	Maryam Rakhshandehroo
title	Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
title_short	Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
title_full	Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
title_fullStr	Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
title_full_unstemmed	Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
title_sort	comparative analysis of gene regulation by the transcription factor pparalpha between mouse and human.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/dc388ba769634e7492dbb1ea64b79ce8
work_keys_str_mv	AT maryamrakhshandehroo comparativeanalysisofgeneregulationbythetranscriptionfactorpparalphabetweenmouseandhuman AT guidohooiveld comparativeanalysisofgeneregulationbythetranscriptionfactorpparalphabetweenmouseandhuman AT michaelmuller comparativeanalysisofgeneregulationbythetranscriptionfactorpparalphabetweenmouseandhuman AT sanderkersten comparativeanalysisofgeneregulationbythetranscriptionfactorpparalphabetweenmouseandhuman
_version_	1718413831460356096

Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.

Ejemplares similares