Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor γ

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 Müller, Guido J Hooiveld, Sander Kersten

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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 γ (PPARγ), as demonstrated using PPARγ antagonist, PPARγ knockdown, 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 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 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.
OriginalsprogEngelsk
TidsskriftMolecular and Cellular Biology
Vol/bind33
Udgave nummer7
Sider (fra-til)1303-16
Antal sider14
ISSN0270-7306
DOI
StatusUdgivet - 2013

Fingeraftryk

Volatile Fatty Acids
Colon
angiopoietin 4
Inulin
Cytoplasmic and Nuclear Receptors
Adipocytes
Transcriptional Activation
Fermentation

Citer dette

Alex, Sheril ; Lange, Katja ; Amolo, Tom ; Grinstead, Jeffrey S ; Haakonsson, Anders K ; Szalowska, Ewa ; Koppen, Arjen ; Mudde, Karin ; Haenen, Daniëlle ; Al-Lahham, Sa'ad ; Roelofsen, Han ; Houtman, René ; van der Burg, Bart ; Mandrup, Susanne ; Bonvin, Alexandre M J J ; Kalkhoven, Eric ; Müller, Michael ; Hooiveld, Guido J ; Kersten, Sander. / Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor γ. I: Molecular and Cellular Biology. 2013 ; Bind 33, Nr. 7. s. 1303-16.
@article{36ec0ef5bc4747158722d1d1613d13ef,
title = "Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor γ",
abstract = "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 γ (PPARγ), as demonstrated using PPARγ antagonist, PPARγ knockdown, 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 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 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.",
author = "Sheril Alex and Katja Lange and Tom Amolo and Grinstead, {Jeffrey S} and Haakonsson, {Anders K} and Ewa Szalowska and Arjen Koppen and Karin Mudde and Dani{\"e}lle Haenen and Sa'ad Al-Lahham and Han Roelofsen and Ren{\'e} Houtman and {van der Burg}, Bart and Susanne Mandrup and Bonvin, {Alexandre M J J} and Eric Kalkhoven and Michael M{\"u}ller and Hooiveld, {Guido J} and Sander Kersten",
year = "2013",
doi = "10.1128/MCB.00858-12",
language = "English",
volume = "33",
pages = "1303--16",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "7",

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Alex, S, Lange, K, Amolo, T, Grinstead, JS, Haakonsson, AK, Szalowska, E, Koppen, A, Mudde, K, Haenen, D, Al-Lahham, S, Roelofsen, H, Houtman, R, van der Burg, B, Mandrup, S, Bonvin, AMJJ, Kalkhoven, E, Müller, M, Hooiveld, GJ & 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, bind 33, nr. 7, s. 1303-16. https://doi.org/10.1128/MCB.00858-12

Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor γ. / Alex, Sheril; Lange, Katja; Amolo, Tom; Grinstead, Jeffrey S; Haakonsson, Anders K; Szalowska, Ewa; Koppen, Arjen; Mudde, Karin; Haenen, Daniëlle; Al-Lahham, Sa'ad; Roelofsen, Han; Houtman, René; van der Burg, Bart; Mandrup, Susanne; Bonvin, Alexandre M J J; Kalkhoven, Eric; Müller, Michael; Hooiveld, Guido J; Kersten, Sander.

I: Molecular and Cellular Biology, Bind 33, Nr. 7, 2013, s. 1303-16.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor γ

AU - Alex, Sheril

AU - Lange, Katja

AU - Amolo, Tom

AU - Grinstead, Jeffrey S

AU - Haakonsson, Anders K

AU - Szalowska, Ewa

AU - Koppen, Arjen

AU - Mudde, Karin

AU - Haenen, Daniëlle

AU - Al-Lahham, Sa'ad

AU - Roelofsen, Han

AU - Houtman, René

AU - van der Burg, Bart

AU - Mandrup, Susanne

AU - Bonvin, Alexandre M J J

AU - Kalkhoven, Eric

AU - Müller, Michael

AU - Hooiveld, Guido J

AU - Kersten, Sander

PY - 2013

Y1 - 2013

N2 - 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 γ (PPARγ), as demonstrated using PPARγ antagonist, PPARγ knockdown, 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 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 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.

AB - 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 γ (PPARγ), as demonstrated using PPARγ antagonist, PPARγ knockdown, 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 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 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.

U2 - 10.1128/MCB.00858-12

DO - 10.1128/MCB.00858-12

M3 - Journal article

VL - 33

SP - 1303

EP - 1316

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 7

ER -