title: Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).
abstract: Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid.
authors: School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK. Electronic address: kerstin.ziegler@uhi.ac.uk.
authors: Kerstin
authors: K
authors: Ziegler
authors: School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK. Electronic address: A.Kerimi@leeds.ac.uk.
authors: Asimina
authors: A
authors: Kerimi
authors: Nestlé Research Center, CH-1000 Lausanne, Switzerland. Electronic address: laure.poquet@rdls.nestle.com.
authors: Laure
authors: L
authors: Poquet
authors: School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK. Electronic address: G.Williamson@leeds.ac.uk.
authors: Gary
authors: G
authors: Williamson
mesh_terms: D001693:Biological Transport, Active / Q000187:drug effects; D020148:Butyric Acid / Q000494:pharmacology*; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003373:Coumaric Acids / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000096:biosynthesis* / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects*; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D020148:Butyric Acid; D003373:Coumaric Acids; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human; C004999:ferulic acid
keywords: Butyric acid; Caco-2; Ferulic acid; Intestine; MCT; Short chain fatty acids