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Short chain fatty acids stimulate Angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating PPARγ
MedLine Citation:
PMID:  23339868     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Angiopoietin-like protein 4 (ANGPTL4/FIAF) has been proposed as circulating mediator between the gut microbiota and fat storage. Here we show that transcription and secretion of ANGPTL4 in human T84 and HT-29 colon adenocarcinoma cells is highly induced by physiological concentrations of short chain fatty acids (SCFA). SCFA induce ANGPTL4 by activating the nuclear receptor PPARγ, as demonstrated using PPARγ antagonist, PPARγ knock-down, and transactivation assays, which show activation of PPARγ but not PPARα and PPARδ by SCFA. At concentrations required for PPARγ activation and ANGPTL4 induction in colon adenocarcinoma cells, 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. Consistent with the notion that fermentation leads to PPAR activation in vivo, feeding mice a diet rich in inulin induced PPAR target genes and pathways in the colon. We conclude that 1) SCFA potently stimulate ANGPTL4 synthesis in human colon adenocarcinoma cells; 2) SCFA transactivate and bind to PPARγ. Our data point to activation of PPARs as a novel mechanism of gene regulation by SCFA in the colon, in addition to other mechanisms of action of SCFA.
Authors:
Sheril Alex; Katja Lange; Tom Amolo; Jeffrey S Grinstead; Anders K Haakonsson; Ewa Szalowska; Arjen Koppen; Karin Mudde; Daniëlle Haenen; Sa'ad Al-Lahham; Han Roelofsen; René Houtman; Bart van der Burg; Susanne Mandrup; Alexandre M J J Bonvin; Eric Kalkhoven; Michael Muller; Guido J Hooiveld; Sander Kersten
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-22
Journal Detail:
Title:  Molecular and cellular biology     Volume:  -     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Nutrition, Metabolism and Genomics group, Wageningen University, Bomenweg 2, 6703HD, Wageningen, the Netherlands.
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