help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on December 15, 2005
Endocrinology, doi:10.1210/en.2005-1132
A more recent version of this article appeared on March 1, 2006
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
147/3/1508    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Patsouris, D.
Right arrow Articles by Kersten, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Patsouris, D.
Right arrow Articles by Kersten, S.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*GLUCOSE

Submitted on September 2, 2005
Accepted on December 7, 2005

PPAR{alpha} mediates the effects of high fat diet on hepatic gene expression

David Patsouris, Janardan K. Reddy, Michael Müller, and Sander Kersten*

Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, PO BOX 8129, 6700 EV Wageningen, the Netherlands; Department of Pathology, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, U.S.A.

* To whom correspondence should be addressed. E-mail: sander.kersten{at}wur.nl.

Peroxisome proliferators activated receptors are transcription factors involved in the regulation of numerous metabolic processes. The PPAR{alpha} isotype is abundant in liver and activated by fasting. However, it is not very clear what other nutritional conditions activate PPAR{alpha}. To examine whether PPAR{alpha} mediates the effects of chronic high fat feeding, wild-type and PPAR{alpha} null mice were fed a low fat diet (LFD) or high fat diet (HFD) for 26 weeks. HFD and PPAR{alpha} deletion independently increased liver triglycerides. Furthermore, in wild-type mice HFD was associated with a significant increase in hepatic PPAR{alpha} mRNA and plasma free fatty acids, leading to a PPAR{alpha}-dependent increase in expression of PPAR{alpha} marker genes CYP4A10 and CYP4A14. Micro-array analysis revealed that HFD increased hepatic expression of characteristic PPAR{alpha} target genes involved in fatty acid oxidation in a PPAR{alpha}-dependent manner, although to a lesser extent than fasting or Wy14643. According to micro-array, there may be functional compensation for PPAR{alpha} in PPAR{alpha} null mice. Remarkably, in PPAR{alpha} null mice on HFD, PPAR{gamma} mRNA was 20-fold elevated compared with wild-type mice fed a LFD, reaching expression levels of PPAR{alpha} in normal mice. Adenoviral over-expression of PPAR{gamma} in liver indicated that PPAR{gamma} can up-regulate genes involved in lipo/adipogenesis but also characteristic PPAR{alpha} targets involved in fatty acid oxidation. It is concluded that 1) PPAR{alpha} and PPAR{alpha}-signaling are activated in liver by chronic high fat feeding 2) PPAR{gamma} may compensate for PPAR{alpha} in PPAR{alpha} null mice on HFD.
Key words: PPAR • High Fat Diet • Glucose metabolism • Triglycerides • Free Fatty Acids • Liver




This article has been cited by other articles:


Home page
 Physiol. GenomicsHome page
W. Rodenburg, A. G. Heidema, J. M. A. Boer, I. M. J. Bovee-Oudenhoven, E. J. M. Feskens, E. C. M. Mariman, and J. Keijer
A framework to identify physiological responses in microarray-based gene expression studies: selection and interpretation of biologically relevant genes
Physiol Genomics, October 8, 2008; 33(1): 78 - 90.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
J. B. Lockridge, M. L. Sailors, D. J. Durgan, O. Egbejimi, W. J. Jeong, M. S. Bray, W. C. Stanley, and M. E. Young
Bioinformatic profiling of the transcriptional response of adult rat cardiomyocytes to distinct fatty acids
J. Lipid Res., July 1, 2008; 49(7): 1395 - 1408.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
M. B. Rosen, B. D. Abbott, D. C. Wolf, J. C. Corton, C. R. Wood, J. E. Schmid, K. P. Das, R. D. Zehr, E. T. Blair, and C. Lau
Gene Profiling in the Livers of Wild-type and PPAR{alpha}-Null Mice Exposed to Perfluorooctanoic Acid
Toxicol Pathol, June 1, 2008; 36(4): 592 - 607.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
Y. Tanaka, L. M. Aleksunes, R. L. Yeager, M. A. Gyamfi, N. Esterly, G. L. Guo, and C. D. Klaassen
NF-E2-Related Factor 2 Inhibits Lipid Accumulation and Oxidative Stress in Mice Fed a High-Fat Diet
J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 655 - 664.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
E. Grasselli, L. Canesi, A. Voci, R. De Matteis, I. Demori, E. Fugassa, and L. Vergani
Effects of 3,5-Diiodo-L-Thyronine Administration on the Liver of High Fat Diet-Fed Rats
Experimental Biology and Medicine, May 1, 2008; 233(5): 549 - 557.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. M. Hebbachi, B. L. Knight, D. Wiggins, D. D. Patel, and G. F. Gibbons
Peroxisome Proliferator-activated Receptor {alpha} Deficiency Abolishes the Response of Lipogenic Gene Expression to Re-feeding: RESTORATION OF THE NORMAL RESPONSE BY ACTIVATION OF LIVER X RECEPTOR {alpha}
J. Biol. Chem., February 22, 2008; 283(8): 4866 - 4876.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. T. Wunderlich, T. Luedde, S. Singer, M. Schmidt-Supprian, J. Baumgartl, P. Schirmacher, M. Pasparakis, and J. C. Bruning
Hepatic NF-{kappa}B essential modulator deficiency prevents obesity-induced insulin resistance but synergizes with high-fat feeding in tumorigenesis
PNAS, January 29, 2008; 105(4): 1297 - 1302.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
V. Pagmantidis, C. Meplan, E. M van Schothorst, J. Keijer, and J. E Hesketh
Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases the expression of lymphocyte protein biosynthesis genes
Am. J. Clinical Nutrition, January 1, 2008; 87(1): 181 - 189.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
M. Bunger, H. M. van den Bosch, J. van der Meijde, S. Kersten, G. J. E. J. Hooiveld, and M. Muller
Genome-wide analysis of PPAR{alpha} activation in murine small intestine
Physiol Genomics, July 18, 2007; 30(2): 192 - 204.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. Stienstra, S. Mandard, D. Patsouris, C. Maass, S. Kersten, and M. Muller
Peroxisome Proliferator-Activated Receptor {alpha} Protects against Obesity-Induced Hepatic Inflammation
Endocrinology, June 1, 2007; 148(6): 2753 - 2763.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
P. Ciana, A. Biserni, L. Tatangelo, C. Tiveron, A. F. Sciarroni, L. Ottobrini, and A. Maggi
A Novel Peroxisome Proliferator-Activated Receptor Responsive Element-Luciferase Reporter Mouse Reveals Gender Specificity of Peroxisome Proliferator-Activated Receptor Activity in Liver
Mol. Endocrinol., February 1, 2007; 21(2): 388 - 400.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
W. O. Ward, D. A. Delker, S. D. Hester, S.-F. Thai, D. C. Wolf, J. W. Allen, and S. Nesnow
Transcriptional Profiles in Liver from Mice Treated with Hepatotumorigenic and Nonhepatotumorigenic Triazole Conazole Fungicides: Propiconazole, Triadimefon, and Myclobutanil
Toxicol Pathol, December 1, 2006; 34(7): 863 - 878.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2005 by The Endocrine Society