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Molecular analysis of the effect of short-chain fatty acids on intestinal cell proliferation

Published online by Cambridge University Press:  05 March 2007

Herve M. Blottiere ,
Bruno Buecher ,
Jean-Paul Galmiche  and
Christine Cherbut
Herve M. Blottiere*
Affiliation:
Human Nutrition Research Centre of Nantes, INRA-UFDNH, C.H. U. Hotel-Dieu, place A. Ricordeau, 44035, Nantes cedex 01, France
Bruno Buecher
Affiliation:
Human Nutrition Research Centre of Nantes, INSERM U539, C.H. U. Hotel-Dieu, place A. Ricordeau, 44035, Nantes cedex 01, France
Jean-Paul Galmiche
Affiliation:
Human Nutrition Research Centre of Nantes, INSERM U539, C.H. U. Hotel-Dieu, place A. Ricordeau, 44035, Nantes cedex 01, France
Christine Cherbut
Affiliation:
Human Nutrition Research Centre of Nantes, INRA-UFDNH, C.H. U. Hotel-Dieu, place A. Ricordeau, 44035, Nantes cedex 01, France
*
*Corresponding author: Dr Herve M. Blottiere, Present address: Nutrition and Food Security Unit, INRA, Centre de Recherche de Jouy, Domaine de Vilvert, 78352 Jouy en Josas cedex, France, fax +33 1 34 65 23 11, hblot@diamant.jouy.inra.fr
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Abstract

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Short-chain fatty acids (SCFA), particularly butyrate, were shown to regulate cell proliferation in vitro and in vivo. Indeed, butyrate is the major fuel for colonic epithelial cells, and it can influence cell proliferation through the release of growth factors or gastrointestinal peptides such as gastrin, or through modulation of mucosal blood flow. Lastly, SCFA can act directly on genes regulating cell proliferation, and butyrate is the main SCFA to display such an effect. Butyrate inhibits histone deacetylase, which will allow histone hyperacetylation. Such hyperacetylation leads to transcription of several genes, including p21/Cipl. Moreover, it will allow cyclin D3 hyper-expression by inhibiting its degradation. The induction of the cyclin-dependent kinase inhibitory protein p21/Cipl accounts for cell arrest in the Gl phase of the cell cycle. However, in the absence of p21 other mechanisms are initiated, leading to inhibition of cell proliferation.

Keywords

ButyrateColonCell cyclep21/CiplCyclin D3
Type
Session: Short-chain fatty acids
Information
Proceedings of the Nutrition Society , Volume 62 , Issue 1 , February 2003 , pp. 101 - 106
Copyright
Copyright © The Nutrition Society 2003

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