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Status |
Public on Mar 11, 2013 |
Title |
Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colonocytes by selective PPARγ modulation |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Angiopoietin-like protein 4 (ANGPTL4, also referred to as Fiaf) has been proposed as a circulating mediator between the gut microbiota and fat storage in adipose tissue. Very little is known about the mechanisms of regulation of ANGPTL4 in the colon. Here we show that transcription and subsequent secretion of ANGPTL4 in human T84 and HT-29 colonocytes is highly induced by physiological concentrations of products of bacterial fermentation, the short-chain fatty acids. Short-chain fatty acids induce ANGPTL4 by activating the nuclear receptor PPARγ, as shown by microarray, transactivation assays, coactivator peptide recruitment assay, and use of PPARγ antagonist. At concentrations required for PPARγ activation and ANGPTL4 induction in colonocytes, SCFA do not stimulate PPARγ in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPARγ modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modelling. It can be concluded that 1) SCFA potently stimulate ANGPTL4 synthesis in human colonocytes, and 2) SCFA transactivate and bind to PPARγ by serving as selective PPAR modulators. Our data point to activation of PPARγ as a novel mechanism of gene regulation by SCFA in the colon.
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Overall design |
T84 human colonic carcinoma epithelial cells were treated with rosiglitazone (0.1 uM) or butyrate (1mM, 8mM) for 24hrs, whereafter gene expression was profiled.
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Contributor(s) |
Alex S, Lange K, Amolo T, Grinstead JS, Szalowska E, Koppen A, Mudde K, Haenen D, Al-Lahham S, Roelofsen H, Houtman R, van den Burg B, Bonvin AM, Kalkhoven E, Muller M, Hooiveld GJ, Kersten S |
Citation(s) |
23339868 |
Submission date |
Sep 07, 2012 |
Last update date |
Nov 08, 2016 |
Contact name |
Guido Hooiveld |
E-mail(s) |
guido.hooiveld@wur.nl
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Organization name |
Wageningen University
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Department |
Div. Human Nutrition & Health
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Lab |
Nutrition, Metabolism & Genomics Group
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Street address |
HELIX, Stippeneng 4
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City |
Wageningen |
ZIP/Postal code |
NL-6708WE |
Country |
Netherlands |
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Platforms (1) |
GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
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Samples (4)
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Relations |
BioProject |
PRJNA174693 |
Supplementary file |
Size |
Download |
File type/resource |
GSE40706_RAW.tar |
17.9 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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