Effect of Synthetic Dietary Triglycerides: A Novel Research Paradigm for Nutrigenomics
Publication Date
February 27, 2008
Journal
PLOS ONE
Authors
Linda M. Sanderson, Philip J. De Groot, Guido J. E. J. Hooiveld, Arjen Koppen, et al
Volume
3
Issue
2
Pages
e1681
DOI
https://dx.plos.org/10.1371/journal.pone.0001681
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0001681
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/18301758
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2244803
Europe PMC
http://europepmc.org/abstract/MED/18301758
Web of Science
000260586500025
Scopus
45249098139
Mendeley
http://www.mendeley.com/research/effect-synthetic-dietary-triglycerides-novel-research-paradigm-nutrigenomics
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Mendeley | Further Information

{"title"=>"Effect of synthetic dietary triglycerides: A novel research paradigm for nutrigenomics", "type"=>"journal", "authors"=>[{"first_name"=>"Linda M.", "last_name"=>"Sanderson", "scopus_author_id"=>"23005801800"}, {"first_name"=>"Philip J.", "last_name"=>"de Groot", "scopus_author_id"=>"21233599500"}, {"first_name"=>"Guido J.E.J.", "last_name"=>"Hooiveld", "scopus_author_id"=>"6603101814"}, {"first_name"=>"Arjen", "last_name"=>"Koppen", "scopus_author_id"=>"8403952000"}, {"first_name"=>"Eric", "last_name"=>"Kalkhoven", "scopus_author_id"=>"6701721272"}, {"first_name"=>"Michael", "last_name"=>"Müller", "scopus_author_id"=>"7404689194"}, {"first_name"=>"Sander", "last_name"=>"Kersten", "scopus_author_id"=>"57192710193"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"351891076", "sgr"=>"45249098139", "issn"=>"19326203", "pmid"=>"18301758", "scopus"=>"2-s2.0-45249098139", "doi"=>"10.1371/journal.pone.0001681", "isbn"=>"1932-6203 (Electronic)"}, "id"=>"d0b9315d-2aef-3be6-a121-bbff8ef25752", "abstract"=>"BACKGROUND: The effect of dietary fats on human health and disease are likely mediated by changes in gene expression. Several transcription factors have been shown to respond to fatty acids, including SREBP-1c, NF-kappaB, RXRs, LXRs, FXR, HNF4alpha, and PPARs. However, it is unclear to what extent these transcription factors play a role in gene regulation by dietary fatty acids in vivo.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Here, we take advantage of a unique experimental design using synthetic triglycerides composed of one single fatty acid in combination with gene expression profiling to examine the effects of various individual dietary fatty acids on hepatic gene expression in mice. We observed that the number of significantly changed genes and the fold-induction of genes increased with increasing fatty acid chain length and degree of unsaturation. Importantly, almost every single gene regulated by dietary unsaturated fatty acids remained unaltered in mice lacking PPARalpha. In addition, the majority of genes regulated by unsaturated fatty acids, especially docosahexaenoic acid, were also regulated by the specific PPARalpha agonist WY14643. Excellent agreement was found between the effects of unsaturated fatty acids on mouse liver versus cultured rat hepatoma cells. Interestingly, using Nuclear Receptor PamChip(R) Arrays, fatty acid- and WY14643-induced interactions between PPARalpha and coregulators were found to be highly similar, although several PPARalpha-coactivator interactions specific for WY14643 were identified.\\n\\nCONCLUSIONS/SIGNIFICANCE: We conclude that the effects of dietary unsaturated fatty acids on hepatic gene expression are almost entirely mediated by PPARalpha and mimic those of synthetic PPARalpha agonists in terms of regulation of target genes and molecular mechanism. Use of synthetic dietary triglycerides may provide a novel paradigm for nutrigenomics research.", "link"=>"http://www.mendeley.com/research/effect-synthetic-dietary-triglycerides-novel-research-paradigm-nutrigenomics", "reader_count"=>49, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>2, "Researcher"=>10, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>9, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>2, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>2, "Researcher"=>10, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>9, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>2, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>10, "Agricultural and Biological Sciences"=>29, "Arts and Humanities"=>1, "Chemistry"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>29}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Netherlands"=>2, "United Kingdom"=>1, "Slovakia"=>1, "France"=>1}, "group_count"=>1}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/936229"], "description"=>"<p>Bars show number of up- (upper panel) and downregulated (lower panel) probesets in the different treatment groups. The number of probesets regulated by unsaturated fatty acids in a PPARα-dependent manner (light bars, not changed in the PPARα −/− mouse), or PPARα-independent manner (dark bars, changed in wild-type and PPARα −/− mice) are shown, with percentage PPARα dependence indicated. Probesets were considered statistically significantly regulated if P<0.01.</p>", "links"=>[], "tags"=>["dietary", "unsaturated", "fatty"], "article_id"=>606672, "categories"=>["Computational Biology", "Genetics", "Neuroscience", "Cell Biology", "Physiology", "Molecular Biology"], "users"=>["Linda M. Sanderson", "Philip J. de Groot", "Guido J. E. J. Hooiveld", "Arjen Koppen", "Eric Kalkhoven", "Michael Müller", "Sander Kersten"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001681.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PPAR_945_dependent_regulation_of_gene_expression_by_dietary_unsaturated_fatty_acids_/606672", "title"=>"PPARα-dependent regulation of gene expression by dietary unsaturated fatty acids.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-27 01:51:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/461500", "https://ndownloader.figshare.com/files/461513", "https://ndownloader.figshare.com/files/461522", "https://ndownloader.figshare.com/files/461532", "https://ndownloader.figshare.com/files/461537", "https://ndownloader.figshare.com/files/461545", "https://ndownloader.figshare.com/files/461558"], "description"=>"<div><h3>Background</h3><p>The effect of dietary fats on human health and disease are likely mediated by changes in gene expression. Several transcription factors have been shown to respond to fatty acids, including SREBP-1c, NF-κB, RXRs, LXRs, FXR, HNF4α, and PPARs. However, it is unclear to what extent these transcription factors play a role in gene regulation by dietary fatty acids <em>in vivo</em>.</p><h3>Methodology/Principal Findings</h3><p>Here, we take advantage of a unique experimental design using synthetic triglycerides composed of one single fatty acid in combination with gene expression profiling to examine the effects of various individual dietary fatty acids on hepatic gene expression in mice. We observed that the number of significantly changed genes and the fold-induction of genes increased with increasing fatty acid chain length and degree of unsaturation. Importantly, almost every single gene regulated by dietary unsaturated fatty acids remained unaltered in mice lacking PPARα. In addition, the majority of genes regulated by unsaturated fatty acids, especially docosahexaenoic acid, were also regulated by the specific PPARα agonist WY14643. Excellent agreement was found between the effects of unsaturated fatty acids on mouse liver versus cultured rat hepatoma cells. Interestingly, using Nuclear Receptor PamChip® Arrays, fatty acid- and WY14643-induced interactions between PPARα and coregulators were found to be highly similar, although several PPARα-coactivator interactions specific for WY14643 were identified.</p><h3>Conclusions/Significance</h3><p>We conclude that the effects of dietary unsaturated fatty acids on hepatic gene expression are almost entirely mediated by PPARα and mimic those of synthetic PPARα agonists in terms of regulation of target genes and molecular mechanism. Use of synthetic dietary triglycerides may provide a novel paradigm for nutrigenomics research.</p></div>", "links"=>[], "tags"=>["synthetic", "dietary", "paradigm", "nutrigenomics"], "article_id"=>150946, "categories"=>["Biological Sciences", "Genetics", "Neuroscience", "Cell Biology", "Physiology", "Molecular Biology"], "users"=>["Linda M. Sanderson", "Philip J. de Groot", "Guido J. E. J. Hooiveld", "Arjen Koppen", "Eric Kalkhoven", "Michael Müller", "Sander Kersten"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0001681.s001", "https://dx.doi.org/10.1371/journal.pone.0001681.s002", "https://dx.doi.org/10.1371/journal.pone.0001681.s003", "https://dx.doi.org/10.1371/journal.pone.0001681.s004", "https://dx.doi.org/10.1371/journal.pone.0001681.s005", "https://dx.doi.org/10.1371/journal.pone.0001681.s006", "https://dx.doi.org/10.1371/journal.pone.0001681.s007"], "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effect_of_Synthetic_Dietary_Triglycerides_A_Novel_Research_Paradigm_for_Nutrigenomics/150946", "title"=>"Effect of Synthetic Dietary Triglycerides: A Novel Research Paradigm for Nutrigenomics", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2008-02-27 00:15:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/936155"], "description"=>"<p>Wild-type and PPARα −/− mice fasted for 4 hours were given a single oral dose of different synthetic triglycerides composed of one single unsaturated fatty acid (400 µl), or one of the PPARα agonists WY14643 or fenofibrate (4 mg). After 6h, the livers were used for gene expression profiling using Affymetrix Mouse Genome 430 2.0 Microarrays (∼45000 probesets) on biological replicates. CMC = carboxymethyl cellulose.</p>", "links"=>[], "tags"=>["dietary"], "article_id"=>606601, "categories"=>["Computational Biology", "Genetics", "Neuroscience", "Cell Biology", "Physiology", "Molecular Biology"], "users"=>["Linda M. Sanderson", "Philip J. de Groot", "Guido J. E. J. Hooiveld", "Arjen Koppen", "Eric Kalkhoven", "Michael Müller", "Sander Kersten"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001681.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_representation_of_dietary_intervention_/606601", "title"=>"Schematic representation of dietary intervention.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-27 01:50:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/936420"], "description"=>"<p>(A) Genes involved in mitochondrial fatty acid oxidation. (B) Genes involved in peroxisomal fatty acid oxidation. The heatmaps were generated directly from the microarray data, using for each probeset the mean signal from 4–5 biological replicates. The grayscale represents fold-induction relative to wild-type control, which was set at 1. Only probesets showing significant (P<0.01) upregulation by WY14643 were included in the analysis. A list of probesets belonging to the functional class of mitochondrial fatty acid oxidation can be found at <a href=\"http://nutrigene.4t.com/microarray/ppar2007\" target=\"_blank\">http://nutrigene.4t.com/microarray/ppar2007</a>.</p>", "links"=>[], "tags"=>["induction", "genes", "fatty", "oxidation", "dietary"], "article_id"=>606858, "categories"=>["Computational Biology", "Genetics", "Neuroscience", "Cell Biology", "Physiology", "Molecular Biology"], "users"=>["Linda M. Sanderson", "Philip J. de Groot", "Guido J. E. J. Hooiveld", "Arjen Koppen", "Eric Kalkhoven", "Michael Müller", "Sander Kersten"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001681.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_induction_of_genes_involved_in_fatty_acid_oxidation_between_various_dietary_fatty_acids_/606858", "title"=>"Differential induction of genes involved in fatty acid oxidation between various dietary fatty acids.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-27 01:54:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/936309"], "description"=>"<p>(A) Venn diagrams showing the overlap in up- (left panel) and downregulated (right panel) genes after treatment with WY14643, C22:6 and C18:1. Genes were considered statistically significantly regulated if P<0.01. (B) Scatter plots demonstrating similarities in gene regulation between C22:6 and WY14643. Graphs show fold change in gene expression after treatment with WY14643 compared to C22:6 and C18:1. Genes that are upregulated disproportionally strongly by WY14643 (<i>Cd36</i>, <i>Fabp4</i> (<i>aP2</i>), and <i>Cpt1b</i>), or by C22:6 (<i>Prlr</i> and <i>Txnip</i>) are marked. In constructing the scatter plots, all probesets left after IQR-filtering were used. (C) Overlap in overrepresented Gene Ontology classes between C22:6, C18:1, and WY14643, based on a functional class score (FCS) method. The GO class unique to C22:6 and C18:1 is GO:0016070 (RNA metabolism), whereas the GO classes unique to C18:1 are GO:0007409 (axonogenesis) and GO:0016072 (rRNA metabolism).</p>", "links"=>[], "tags"=>["dietary", "unsaturated", "fatty", "acids", "synthetic", "agonist"], "article_id"=>606747, "categories"=>["Computational Biology", "Genetics", "Neuroscience", "Cell Biology", "Physiology", "Molecular Biology"], "users"=>["Linda M. Sanderson", "Philip J. de Groot", "Guido J. E. J. Hooiveld", "Arjen Koppen", "Eric Kalkhoven", "Michael Müller", "Sander Kersten"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001681.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Similarities_between_two_dietary_unsaturated_fatty_acids_and_the_synthetic_PPAR_945_agonist_WY14643_/606747", "title"=>"Similarities between two dietary unsaturated fatty acids and the synthetic PPARα agonist WY14643.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-27 01:52:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/936596"], "description"=>"<p>The Nuclear Receptor PamChip® assay was used to measure the interaction between PPARα and immobilized peptides corresponding to specific coregulator-nuclear receptor binding regions. Measurements were performed in the presence of control (EtOH), WY14643 (5 µM) or C22:6 (100 µM). Arrows point to those co-activators selectively recruited by WY14643 but not C22:6. All images were taken after 100 msec exposure time.</p>", "links"=>[], "tags"=>["recruitment", "assay", "wy14643"], "article_id"=>607037, "categories"=>["Computational Biology", "Genetics", "Neuroscience", "Cell Biology", "Physiology", "Molecular Biology"], "users"=>["Linda M. Sanderson", "Philip J. de Groot", "Guido J. E. J. Hooiveld", "Arjen Koppen", "Eric Kalkhoven", "Michael Müller", "Sander Kersten"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001681.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cofactor_recruitment_assay_with_WY14643_and_C22_6_/607037", "title"=>"Cofactor recruitment assay with WY14643 and C22:6.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-27 01:57:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/936517"], "description"=>"<p>mRNA expression of three genes (<i>Pdk4</i>, <i>Ehhadh</i> and <i>Cyp4A14</i>) was determined in mouse liver and in rat hepatoma FAO cells using quantitative real-time PCR. Results are shown as fold-change compared to control group. Error bars represent SD.</p>", "links"=>[], "tags"=>["fatty", "acid-dependent"], "article_id"=>606959, "categories"=>["Computational Biology", "Genetics", "Neuroscience", "Cell Biology", "Physiology", "Molecular Biology"], "users"=>["Linda M. Sanderson", "Philip J. de Groot", "Guido J. E. J. Hooiveld", "Arjen Koppen", "Eric Kalkhoven", "Michael Müller", "Sander Kersten"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001681.g005", "stats"=>{"downloads"=>3, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Close_agreement_between_fatty_acid_dependent_gene_regulation_in_vivo_and_in_vitro_/606959", "title"=>"Close agreement between fatty acid-dependent gene regulation <i>in vivo</i> and <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-27 01:55:59"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"26", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"26", "full-text"=>"26", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"10", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"15", "full-text"=>"20", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"14", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"11", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}

Relative Metric

{"start_date"=>"2008-01-01T00:00:00Z", "end_date"=>"2008-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[324, 674, 863, 1015, 1146, 1259, 1360, 1452, 1540, 1621, 1704, 1776, 1843, 1905, 1968, 2029, 2097, 2162, 2233, 2289, 2352, 2412, 2476, 2538, 2601, 2655, 2714, 2777, 2841, 2894, 2946, 2998, 3047, 3103, 3151, 3201, 3258, 3317, 3369, 3424, 3471, 3521, 3583, 3625, 3687, 3743, 3788, 3838, 3896, 3953, 4015, 4075, 4148, 4201, 4275, 4347, 4420, 4486, 4535, 4592, 4660, 4731, 4792, 4845, 4901, 4971, 5027, 5089, 5148, 5200, 5261, 5318, 5374]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[303, 661, 845, 1003, 1135, 1248, 1352, 1439, 1532, 1618, 1691, 1765, 1831, 1902, 1969, 2028, 2098, 2159, 2234, 2294, 2356, 2423, 2483, 2548, 2615, 2682, 2743, 2796, 2853, 2907, 2970, 3025, 3078, 3138, 3197, 3243, 3307, 3351, 3420, 3468, 3519, 3569, 3625, 3688, 3739, 3799, 3850, 3911, 3961, 4009, 4075, 4137, 4194, 4263, 4329, 4393, 4449, 4501, 4566, 4638, 4706, 4761, 4828, 4898, 4948, 4999, 5040, 5107, 5170, 5226, 5292, 5352, 5434]}]}
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