Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 530131
Title Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colonocytes by selective PPARγ modulation
Author(s) Alex, Sheril; Lange, Katja; Amolo, Tom; Grinstead, Jeffrey S.; Szalowska, Ewa; Koppen, Arjen; Mudde, Karin; Haenen, Danielle; Al-Lahham, S.; Roelofsen, Han; Houtman, René; Burg, Bart van den; Bonvin, Alexandre M.; Kalkhoven, Eric; Muller, Michael; Hooiveld, Guido; Kersten, Sander
Department(s) Human Nutrition (HNE)
Chair Nutrition Metabolism and Genomics
RIKILT - BU Toxicology Bioassays & Novel Foods
Publication type Dataset
Publication year 2013
Keyword(s) Homo sapiens - GSE40706 - PRJNA174693
Abstract 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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