Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.
Maryam Rakhshandehroo,Linda M. Sanderson,Merja Matilainen,Rinke Stienstra,Carsten Carlberg,Philip J. de Groot,Michael Müller,Sander Kersten +7 more
TLDR
In this paper, the power of transcriptional profiling to uncover novel PPARα-regulated genes and pathways in liver was illustrated, using an in silico screening approach, one or more PPAR response elements were identified in each of these genes.Abstract:
PPARα is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARα in hepatic lipid metabolism, many PPARα-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARα-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARα target genes, livers from several animal studies in which PPARα was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARα-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARα-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein β polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (HSL, Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARα agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARα. Our study illustrates the power of transcriptional profiling to uncover novel PPARα-regulated genes and pathways in liver.read more
Citations
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Journal ArticleDOI
Peroxisome Proliferator-Activated Receptor Alpha Target Genes
TL;DR: An overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPAR α target genes is presented.
Journal ArticleDOI
Paternally Induced Transgenerational Environmental Reprogramming of Metabolic Gene Expression in Mammals
Benjamin R. Carone,Lucas Fauquier,Naomi Habib,Jeremy M. Shea,Caroline E. Hart,Ruowang Li,Christoph Bock,Christoph Bock,Chengjian Li,Hongcang Gu,Phillip D. Zamore,Alexander Meissner,Alexander Meissner,Zhiping Weng,Hans A. Hofmann,Nir Friedman,Oliver J. Rando +16 more
TL;DR: It is indicated that parental diet can affect cholesterol and lipid metabolism in offspring and define a model system to study environmental reprogramming of the heritable epigenome.
Journal ArticleDOI
Hepatocyte-Specific Deletion of SIRT1 Alters Fatty Acid Metabolism and Results in Hepatic Steatosis and Inflammation
TL;DR: It is demonstrated that hepatic SIRT1 regulates lipid homeostasis by positively regulating peroxisome proliferators-activated receptor alpha (PPARalpha), a nuclear receptor that mediates the adaptive response to fasting and starvation and that pharmacological activation of Sirt1 may be important for the prevention of obesity-associated metabolic diseases.
Journal ArticleDOI
Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease.
TL;DR: The transcriptional activation and repression mechanisms by PPAR α, the spectrum of target genes and chromatin-binding maps from recent genome-wide studies, are discussed, paying particular attention to PPARα-regulation of hepatic fatty acid and plasma lipoprotein metabolism during nutritional transition, and of the inflammatory response.
Journal ArticleDOI
Integrated physiology and systems biology of PPARα.
TL;DR: This review addresses the functional role of PPARα in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPAR α, with a focus on liver.
References
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Béatrice Desvergne,Walter Wahli +1 more
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Robert Zimmermann,Juliane G. Strauss,Guenter Haemmerle,Gabriele Schoiswohl,Ruth Birner-Gruenberger,Monika Riederer,Achim Lass,Georg Neuberger,Frank Eisenhaber,Albin Hermetter,Rudolf Zechner +10 more
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Journal ArticleDOI
Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data.
Manhong Dai,Pinglang Wang,Andrew D. Boyd,Georgi Kostov,Brian D. Athey,Edward G. Jones,William E. Bunney,Richard M. Myers,Terry P. Speed,Huda Akil,Stanley J. Watson,Fan-Dong Meng +11 more
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Peroxisome proliferator–activated receptor α mediates the adaptive response to fasting
Sander Kersten,Josiane Seydoux,Jeffrey M. Peters,Frank J. Gonzalez,Béatrice Desvergne,Walter Wahli +5 more
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