Role of short-chain fatty acids in colonic HCO3secretion

2005 ◽  
Vol 288 (6) ◽  
pp. G1217-G1226 ◽  
Author(s):  
Sadasivan Vidyasagar ◽  
Christian Barmeyer ◽  
John Geibel ◽  
Henry J. Binder ◽  
Vazhaikkurichi M. Rajendran
Keyword(s):  
Colonic Mucosa ◽  
Apical Membrane ◽  
Membrane Vesicles ◽  
Anion Channel ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Channel Activity ◽  
Colonic Crypts ◽  
Ph Stat

Luminal isobutyrate, a relatively poor metabolized short-chain fatty acid (SCFA), induces HCO3secretion via a Cl-independent, DIDS-insensitive, carrier-mediated process as well as inhibiting both Cl-dependent and cAMP-induced HCO3secretion. The mechanism(s) responsible for these processes have not been well characterized. HCO3secretion was measured in isolated colonic mucosa mounted in Lucite chambers using pH stat technique and during microperfusion of isolated colonic crypts.14C-labeled butyrate,14C-labeled isobutyrate, and36Cl uptake were also determined by apical membrane vesicles (AMV) isolated from surface and/or crypt cells. Butyrate stimulation of Cl-independent, DIDS-insensitive 5-nitro-3-(3-phenylpropyl-amino)benzoic acid-insensitive HCO3secretion is greater than that by isobutyrate, suggesting that both SCFA transport and metabolism are critical for HCO3secretion. Both lumen and serosal 25 mM butyrate inhibit cAMP-induced HCO3secretion to a comparable degree (98 vs. 90%). In contrast, Cl-dependent HCO3secretion is downregulated by lumen 25 mM butyrate considerably more than by serosal butyrate (98 vs. 37%). Butyrate did not induce HCO3secretion in isolated microperfused crypts, whereas an outward-directed HCO3gradient-driven induced14C-butyrate uptake by surface but not crypt cell AMV. Both36Cl/HCO3exchange and potential-dependent36Cl movement in AMV were inhibited by 96–98% by 20 mM butyrate. We conclude that 1) SCFA-dependent HCO3secretion is the result of SCFA transport across the apical membrane via a SCFA/HCO3exchange more than intracellular SCFA metabolism; 2) SCFA-dependent HCO3secretion is most likely a result of an apical membrane SCFA/HCO3exchange in surface epithelial cells; 3) SCFA downregulates Cl-dependent and cAMP-induced HCO3secretion secondary to SCFA inhibition of apical membrane Cl/HCO3exchange and anion channel activity, respectively.

Three distinct mechanisms of HCO3−secretion in rat distal colon

2004 ◽  
Vol 287 (3) ◽  
pp. C612-C621 ◽  
Author(s):  
Sadasivan Vidyasagar ◽  
Vazhaikkurichi M. Rajendran ◽  
Henry J. Binder
Keyword(s):  
Colonic Mucosa ◽  
Short Chain Fatty Acid ◽  
Channel Blocker ◽  
Apical Membrane ◽  
Anion Channel ◽  
Distal Colon ◽  
Chain Fatty Acid ◽  
Direct Examination ◽  
Rat Distal Colon ◽  
Ph Stat

HCO3−secretion has long been recognized in the mammalian colon, but it has not been well characterized. Although most studies of colonic HCO3−secretion have revealed evidence of lumen Cl−dependence, suggesting a role for apical membrane Cl−/HCO3−exchange, direct examination of HCO3−secretion in isolated crypt from rat distal colon did not identify Cl−-dependent HCO3−secretion but did reveal cAMP-induced, Cl−-independent HCO3−secretion. Studies were therefore initiated to determine the characteristics of HCO3−secretion in isolated colonic mucosa to identify HCO3−secretion in both surface and crypt cells. HCO3−secretion was measured in rat distal colonic mucosa stripped of muscular and serosal layers by using a pH stat technique. Basal HCO3−secretion (5.6 ± 0.03 μeq·h−1·cm−2) was abolished by removal of either lumen Cl−or bath HCO3−; this Cl−-dependent HCO3−secretion was also inhibited by 100 μM DIDS (0.5 ± 0.03 μeq·h−1·cm−2) but not by 5-nitro-3-(3-phenylpropyl-amino)benzoic acid (NPPB), a Cl−channel blocker. 8-Bromo-cAMP induced Cl−-independent HCO3−secretion (and also inhibited Cl−-dependent HCO3−secretion), which was inhibited by NPPB and by glibenclamide, a CFTR blocker, but not by DIDS. Isobutyrate, a poorly metabolized short-chain fatty acid (SCFA), also induced a Cl−-independent, DIDS-insensitive, saturable HCO3−secretion that was not inhibited by NPPB. Three distinct HCO3−secretory mechanisms were identified: 1) Cl−-dependent secretion associated with apical membrane Cl−/HCO3−exchange, 2) cAMP-induced secretion that was a result of an apical membrane anion channel, and 3) SCFA-dependent secretion associated with an apical membrane SCFA/HCO3−exchange.

scholarly journals Nonionic diffusion of short-chain fatty acids across rat colon

1998 ◽  
Vol 274 (3) ◽  
pp. G518-G524 ◽  
Author(s):  
Alan N. Charney ◽  
Ljubisa Micic ◽  
Richard W. Egnor
Keyword(s):  
Apical Membrane ◽  
Distal Colon ◽  
Short Chain Fatty Acids ◽  
Linear Increase ◽  
Short Chain ◽  
Rat Colon ◽  
Ussing Chambers ◽  
Ethanesulfonic Acid ◽  
Ratus Ratus

Short-chain fatty acid (SCFA) transport across the colon may occur by nonionic diffusion and/or via apical membrane SCFA−/[Formula: see text]exchange. To examine the relative importance of these processes, stripped segments of rat ( Ratus ratus) proximal and distal colon were studied in Ussing chambers, and the unidirectional fluxes of radiolabeled SCFA butyrate, propionate, or weakly metabolized isobutyrate were measured. In N-2-hydroxyethylpiperazine- N′-2-ethanesulfonic acid (HEPES) or 1 or 5 mM [Formula: see text] Ringer, decreases in mucosal pH stimulated mucosal-to-serosal flux ( J m→s) of all SCFA, decreases in serosal pH stimulated serosal-to-mucosal flux ( J s→m), and bilateral pH decreases stimulated both fluxes equally. These effects were observed whether the SCFA was present on one or both sides of the tissue, in both proximal and distal colon, in the absence of luminal Na+, and in the presence of either luminal or serosal ouabain. Changes in intracellular pH or intracellular [[Formula: see text]] did not account for the effects of extracellular pH. Luminal Cl− removal, to evaluate the role of apical membrane Cl−/SCFA−exchange, had no effect on J m→s but decreased J s→m 32% at pH 6.5 and 22% at 7.2. Increasing SCFA concentration from 1 to 100 mM, at pH 6.4 or 7.4, caused a linear increase in J m→s. We conclude that SCFA are mainly transported across the rat colon by nonionic diffusion.

Emerging role of nutritional short-chain fatty acids (SCFAs) against cancer via modulation of hematopoiesis

2021 ◽  
pp. 1-18
Author(s):  
Muthu Thiruvengadam ◽  
Umadevi Subramanian ◽  
Baskar Venkidasamy ◽  
Prabhu Thirupathi ◽  
Ramkumar Samynathan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

scholarly journals Short Chain Fatty Acids Effect on Chloride Channel ClC-2 as a Possible Mechanism for Lubiprostone Intestinal Action

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1781
Author(s):  
Marcelo A. Catalán ◽  
Francisca Julio-Kalajzić ◽  
María Isabel Niemeyer ◽  
Luis Pablo Cid ◽  
Francisco V. Sepúlveda
Keyword(s):  
Fatty Acids ◽  
Mammalian Cells ◽  
Anion Channel ◽  
Synthetic Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Physiological Effect ◽  
Short Chain ◽  
Distal Intestine ◽  
Dual Action ◽  
Chain Fatty Acids

Lubiprostone, a 20-carbon synthetic fatty acid used for the treatment of constipation, is thought to act through an action on Cl− channel ClC-2. Short chain fatty acids (SCFAs) are produced and absorbed in the distal intestine. We explore whether SCFAs affect ClC-2, re-examine a possible direct effect of lubiprostone on ClC-2, and use mice deficient in ClC-2 to stringently address the hypothesis that the epithelial effect of lubiprostone targets this anion channel. Patch-clamp whole cell recordings of ClC-2 expressed in mammalian cells are used to assay SCFA and lubiprostone effects. Using chamber measurements of ion current in mice deficient in ClC-2 or CFTR channels served to analyze the target of lubiprostone in the distal intestinal epithelium. Intracellular SCFAs had a dual action on ClC-2, partially inhibiting conduction but, importantly, facilitating the voltage activation of ClC-2. Intra- or extracellular lubiprostone had no effect on ClC-2 currents. Lubiprostone elicited a secretory current across colonic epithelia that was increased in mice deficient in ClC-2, consistent with the channel’s proposed proabsorptive function, but absent from those deficient in CFTR. Whilst SCFAs might exert a physiological effect on ClC-2 as part of their known proabsorptive effect, ClC-2 plays no part in the lubiprostone intestinal effect that appears mediated by CFTR activation.

scholarly journals The role of short chain fatty acids in appetite regulation and energy homeostasis

2015 ◽  
Vol 39 (9) ◽  
pp. 1331-1338 ◽  
Author(s):  
C S Byrne ◽  
E S Chambers ◽  
D J Morrison ◽  
G Frost
Keyword(s):  
Fatty Acids ◽  
Energy Homeostasis ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Appetite Regulation ◽  
Chain Fatty Acids

scholarly journals Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway

2000 ◽  
Vol 279 (5) ◽  
pp. G925-G930 ◽  
Author(s):  
G. Cuche ◽  
J. C. Cuber ◽  
C. H. Malbert
Keyword(s):  
Gastric Motility ◽  
Short Chain Fatty Acid ◽  
Peptide Yy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Maximal Amplitude ◽  
Inhibiting Factor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The aim of this study was to evaluate the nervous and humoral pathways involved in short-chain fatty acid (SCFA)-induced ileal brake in conscious pigs. The role of extrinsic ileal innervation was evaluated after SCFA infusion in innervated and denervated Babkin's ileal loops, and gastric motility was measured with strain gauges. Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) concentrations were evaluated in both situations. The possible involvement of absorbed SCFA was tested by using intravenous infusion of acetate. Ileal SCFA infusion in the intact terminal ileum decreased the amplitude of distal and terminal antral contractions (33 ± 1.2 vs. 49 ± 1.2% of the maximal amplitude recorded before infusion) and increased their frequency (1.5 ± 0.11 vs. 1.3 ± 0.10/min). Similar effects were observed during SCFA infusion in ileal innervated and denervated loops (amplitude, 35 ± 1.0 and 34 ± 0.8 vs. 47 ± 1.3 and 43 ± 1.2%; frequency, 1.4 ± 0.07 and 1.6 ± 0.06 vs. 1.1 ± 0.14 and 1.0 ± 0.12/min). Intravenous acetate did not modify the amplitude and frequency of antral contractions. PYY but not GLP-1 concentrations were increased during SCFA infusion in innervated and denervated loops. In conclusion, ileal SCFA inhibit distal gastric motility by a humoral pathway involving the release of an inhibiting factor, which is likely PYY.

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