Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor γ
| Autor: | Alex, S., Lange, K., Amolo, T., Grinstead, J.S., Haakonsson, A.K., Szalowska, E., Koppen, A., Mudde, K., Haenen, D., Al-Lahham, S., Roelofsen, H., Houtman, R., van der Burg, B., Mandrup, S., Bonvin, A.M.J.J., Kalkhoven, E., Müller, M., Hooiveld, G.J., Kersten, S., NMR Spectroscopy, Dep Scheikunde, Sub NMR Spectroscopy |
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| Přispěvatelé: | Sub NMR Spectroscopy, NMR Spectroscopy |
| Rok vydání: | 2013 |
| Předmět: |
Male
Angptl4 Transcription Genetic Protein-4 Peroxisome proliferator-activated receptor Expression Mice Transactivation In-vitro Plasma 0302 clinical medicine ANGPTL4 Taverne Inhibition chemistry.chemical_classification 0303 health sciences Adipogenesis digestive oral and skin physiology Inulin food and beverages Transcriptional activity Articles Cell biology Ppar-gamma Biochemistry 030220 oncology & carcinogenesis Colonic Neoplasms lipids (amino acids peptides and proteins) HT29 Cells Transcriptional Activation Colon Butyrate Gut microbiota Adenocarcinoma Biology digestive system 03 medical and health sciences Mediator 3T3-L1 Cells Cell Line Tumor Coactivator Angiopoietin-Like Protein 4 Animals Humans Molecular Biology 030304 developmental biology Cell Biology Fatty Acids Volatile digestive system diseases Mice Inbred C57BL PPAR gamma Nuclear receptor chemistry Angiopoietins |
| Zdroj: | Molecular and Cellular Biology, 33(7), 1303. American Society for Microbiology Alex, S, Lange, K, Amolo, T, Grinstead, J S, Haakonsson, A K, Szalowska, E, Koppen, A, Mudde, K, Haenen, D, Al-Lahham, S, Roelofsen, H, Houtman, R, van der Burg, B, Mandrup, S, Bonvin, A M J J, Kalkhoven, E, Müller, M, Hooiveld, G J & Kersten, S 2013, ' Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor γ ', Molecular and Cellular Biology, vol. 33, no. 7, pp. 1303-1316 . https://doi.org/10.1128/MCB.00858-12 |
| ISSN: | 0270-7306 |
| Popis: | Angiopoietin-like protein 4 (ANGPTL4/FIAF) has been proposed as a circulating mediator between the gut microbiota and fat storage. Here, we show that transcription and secretion of ANGPTL4 in human T84 and HT29 colon adenocarcinoma cells is highly induced by physiological concentrations of short-chain fatty acids (SCFA). SCFA induce ANGPTL4 by activating the nuclear receptor peroxisome proliferator activated receptor gamma (PPAR gamma), as demonstrated using PPAR gamma antagonist, PPAR gamma knockdown, and transactivation assays, which show activation of PPAR gamma but not PPAR alpha and PPAR delta by SCFA. At concentrations required for PPAR gamma activation and ANGPTL4 induction in colon adenocarcinoma cells, SCFA do not stimulate PPAR gamma in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPAR gamma modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modeling. 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 (i) SCFA potently stimulate ANGPTL4 synthesis in human colon adenocarcinoma cells and (ii) SCFA transactivate and bind to PPAR gamma. 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. |
| Databáze: | OpenAIRE |
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