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Cited by 266

The DOI matches its Crossref record; 131 of the 131 references it cites were found in a registry or an index.

Short‐Chain Fatty Acid Transporters: Role in Colonic Homeostasis

Open access
Sivaprakasam, Sathish, Bhutia, Yangzom D., Yang, Shengping, Ganapathy, Vadivel·2017·Comprehensive Physiology
DOI 10.1002/cphy.c170014
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Abstract

Short‐chain fatty acids (SCFA; acetate, propionate, and butyrate) are generated in colon by bacterial fermentation of dietary fiber. Though diffusion in protonated form is a significant route, carrier‐mediated mechanisms constitute the major route for the entry of SCFA in their anionic form into colonic epithelium. Several transport systems operate in cellular uptake of SCFA. MCT1 (SLC16A1) and MCT4 (SLC16A3) are H+‐coupled and mediate electroneutral transport of SCFA (H+: SCFA stoichiometry; 1:1). MCT1 is expressed both in the apical membrane and basolateral membrane of colonic epithelium whereas MCT4 specifically in the basolateral membrane. SMCT1 (SLC5A8) and SMCT2 (SLC5A12) are Na+‐coupled; SMCT1‐mediated transport is electrogenic (Na+: SCFA stoichiometry; 2:1) whereas SMCT2‐mediated transport is electroneutral (Na+: SCFA stoichiometry; 1:1). SMCT1 and SMCT2 are expressed exclusively in the apical membrane. An anion‐exchange mechanism also operates in the apical membrane in which SCFA entry in anionic form is coupled to bicarbonate efflux; the molecular identity of this exchanger however remains unknown. All these transporters are subject to regulation, notably by their substrates themselves; this process involves cell‐surface receptors with SCFA as signaling molecules. There are significant alterations in the expression of these transporters in ulcerative colitis and colon cancer. The tumor‐associated changes occur via transcriptional regulation by p53 and HIF1α and by promoter methylation. As SCFA are obligatory for optimal colonic health, the transporters responsible for the entry and transcellular transfer of these bacterial products in colonic epithelium are critical determinants of colonic function under physiological conditions and in disease states. © 2018 American Physiological Society.Compr Physiol 8:299‐314, 2018.

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Metadata

Authors
Sivaprakasam, S., Bhutia, Y. D., Yang, S., & Ganapathy, V.
Venue
Comprehensive Physiology
Publisher
Wiley
Published
2017-12-12
Volume
8
Issue
1
Pages
299-314
ISSN
2040-4603 (ISSN-L)
DOI
10.1002/cphy.c170014
OpenAlex
W2900456357
Cited by
266
References
131
Type
other
Language
en
Open access
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