scholarly journals Physiological concentrations of short-chain fatty acids immediately suppress colonic epithelial permeability

2008 ◽  
Vol 100 (2) ◽  
pp. 297-305 ◽  
Author(s):  
Takuya Suzuki ◽  
Shoko Yoshida ◽  
Hiroshi Hara
Keyword(s):  
Barrier Function ◽  
Lucifer Yellow ◽  
Short Chain Fatty Acids ◽  
Monocarboxylate Transporter ◽  
Phosphatidylinositol 3 Kinase ◽  
Fermentation Products ◽  
Epithelial Barrier Function ◽  
Monocarboxylate Transporter 1 ◽  
Promotive Effect ◽  
Anaesthetized Rats

Colonic fermentation products, SCFA, have various effects on colonic functions. Here, we found that physiological concentrations of SCFA immediately promote epithelial barrier function in the large intestine. Solutions of mixed and individual SCFA were applied to the caecal walls mounted on Ussing-type chambers. Transepithelial electrical resistance (TER) increased rapidly and reached a peak 35 % higher than that in the control specimen within 10 min post application of the SCFA mixture (80 acetate, 40 propionate, 20 butyrate (mmol/l)). The Lucifer yellow permeability, a paracellular transport marker, was dose-dependently reduced by the mixed SCFA, acetate and propionate solutions. Inhibition of monocarboxylate transporter-1 did not influence the increase in TER with acetate; however, lowering the pH (from 7·5 to 5·5) clearly enhanced the effect of acetate. Non-metabolizable, bromo and chloro derivatives of SCFA also increased TER. These results suggest that passive diffusion of SCFA is dominant and the metabolism of SCFA is not required for the promotive effect of SCFA on barrier function. We also observed that individual SCFA dose-dependently increased TER in T84 and Caco-2 cells, which indicates that SCFA directly stimulate epithelial cells. Depletion of membrane cholesterol and inhibitors of phosphatidylinositol-3 kinase and Gq protein attenuated the acetate-mediated promotive effect. Finally, we found that the mucosal application of the SCFA mixture dose-dependently suppressed [3H] mannitol transport from the caecal lumen to the mesenteric blood in the anaesthetized rats. We conclude that physiological concentrations of SCFA immediately enhance barrier function of the colonic epithelium through cholesterol-rich microdomain in the plasma membrane.

Transport of ketone bodies and lactate in the sheep ruminal epithelium by monocarboxylate transporter 1

2002 ◽  
Vol 283 (5) ◽  
pp. G1139-G1146 ◽  
Author(s):  
Frank Müller ◽  
Korinna Huber ◽  
Helga Pfannkuche ◽  
Jörg R. Aschenbach ◽  
Gerhard Breves ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cultured Cells ◽  
Ketone Bodies ◽  
Short Chain Fatty Acids ◽  
Monocarboxylate Transporter ◽  
Monocarboxylate Transporter 1 ◽  
Protein Levels ◽  
Ruminal Epithelium ◽  
Intracellular Metabolism ◽  
Acid Extrusion

Due to intensive intracellular metabolism of short-chain fatty acids, ruminal epithelial cells generate large amounts of d-β-hydroxybutyric acid, acetoacetic acid, and lactic acid. These acids have to be extruded from the cytosol to avoid disturbances of intracellular pH (pHi). To evaluate acid extrusion, pHi was studied in cultured ruminal epithelial cells of sheep using the pH-sensitive fluorescent dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Extracellular addition of d-β-hydroxybutyrate, acetoacetate, or lactate (20 mM) resulted in intracellular acidification. Vice versa, removing extracellulard-β-hydroxybutyrate, acetoacetate, or lactate after preincubation with the respective monocarboxylate induced an increase of pHi. Initial rate of pHi decrease as well as of pHi recovery was strongly inhibited by pCMBS (400 μM) and phloretin (20 μM). Both cultured cells and intact ruminal epithelium were tested for the possible presence of proton-linked monocarboxylate transporter (MCT) on both the mRNA and protein levels. With the use of RT-PCR, mRNA encoding for MCT1 isoform was demonstrated in cultured ruminal epithelial cells and the ruminal epithelium. Immunostaining with MCT1 antibodies intensively labeled cultured ruminal epithelial cells and cells located in the stratum basale of the ruminal epithelium. In conclusion, our data indicate that MCT1 is expressed in the stratum basale of the ruminal epithelium and may function as a main mechanism for removing ketone bodies and lactate together with H+ from the cytosol into the blood.

miR-29a, b and c Regulate SLC5A8 Expression in Intestinal Epithelial Cells

2021 ◽  
Author(s):  
Arivarasu Natarajan Anbazhagan ◽  
Shubha Priyamvada ◽  
Anoop Kumar ◽  
Dulari Jayawardena ◽  
Alip Borthakur ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
In Silico Analysis ◽  
Short Chain Fatty Acids ◽  
Monocarboxylate Transporter ◽  
Luciferase Reporter ◽  
Intestinal Epithelial ◽  
Bacterial Fermentation ◽  
Monocarboxylate Transporter 1 ◽  
Beneficial Effects ◽  
And Function

Short chain fatty acids (SCFAs) produced by bacterial fermentation of dietary fiber exert myriad of beneficial effects including the amelioration of inflammation. SCFAs exist as anions at luminal pH, their entry into the cells depends on the expression and function of monocarboxylate transporters. In this regard, sodium-coupled monocarboxylate transporter-1 (SMCT-1) is one of the major proteins involved in the absorption of SCFA in the mammalian colon. However, very little is known about the mechanisms of regulation of SMCT-1 expression in health and disease. MicroRNAs (miRs) are known to play a key role in modulating gene expression. In silico analysis showed miR-29abc with highest context score and its binding region was conserved among mammals. The 3`-untranslated region (UTR) of human SMCT-1 gene was cloned into pmirGLO vector upstream of luciferase reporter and transiently transfected with miR-29a, b and c mimics into Caco-2 and/or T-84 cells. The presence of UTR of this gene significantly decreased luciferase activity compared to empty vector. Co-transfection with miR-29a, b or c resulted in further decrease in 3`UTR activity of SMCT-1 luciferase constructs. Mimic transfection significantly decreased SMCT-1 protein expression without altering mRNA expression. Further, the expression of miR-29a and c were significantly lower in mouse colon compared to small intestine, consistent with higher levels of SMCT-1 protein in the colon. Our studies demonstrated a novel finding in which miR-29a, b and c down-regulate SMCT-1 expression in colonic epithelial cells and may partly explain the differential expression of these transporters along the length of the GI tract.

scholarly journals Monocarboxylate transporter 1 (MCT1) plays a direct role in short-chain fatty acids absorption in caprine rumen

2006 ◽  
Vol 576 (2) ◽  
pp. 635-647 ◽  
Author(s):  
Doaa Kirat ◽  
Junji Masuoka ◽  
Hideaki Hayashi ◽  
Hidetomo Iwano ◽  
Hiroshi Yokota ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Monocarboxylate Transporter ◽  
Direct Role ◽  
Monocarboxylate Transporter 1 ◽  
Chain Fatty Acids

scholarly journals SCFA transport in rat duodenum

2015 ◽  
Vol 308 (3) ◽  
pp. G188-G197 ◽  
Author(s):  
Izumi Kaji ◽  
Toshihiko Iwanaga ◽  
Masahiko Watanabe ◽  
Paul H. Guth ◽  
Eli Engel ◽  
...  
Keyword(s):  
Bacterial Colonization ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Bacterial Overgrowth ◽  
Short Circuit Current ◽  
Short Chain Fatty Acids ◽  
Duodenal Mucosa ◽  
Monocarboxylate Transporter ◽  
Monocarboxylate Transporter 1 ◽  
Rat Duodenum

Bacterial or ingested food-derived short-chain fatty acids (SCFAs) are present in the duodenal lumen. Acetate, the most abundant SCFA in the foregut lumen, is absorbed immediately after ingestion, although the mechanism by which this absorption occurs is not fully understood. We investigated the distribution and function of candidate SCFA transporters in rat duodenum. The Na+-coupled monocarboxylate transporter-1 (SMCT1) was localized to the brush border, whereas the pH-dependent monocarboxylate transporter (MCT) 1 and MCT4 were localized to the duodenocyte basolateral membrane. In Ussing chambered duodenal mucosa, luminal acetate dose-dependently increased short-circuit current ( Isc) in the presence of serosal bumetanide and indomethacin by a luminal Na+-dependent, ouabain-sensitive mechanism. The Isc response was inhibited dose-dependently by the SMCT1 nonsubstrate inhibitor ibuprofen, consistent with net electrogenic absorption of acetate via SMCT1. Other SCFAs and lactate also increased Isc. Furthermore, duodenal loop perfusion of acetate increased portal venous acetate concentration, inhibited by coperfusion of ibuprofen or a MCT inhibitor. Luminal acetate perfusion increased duodenal HCO3− secretion via capsaicin-sensitive afferent nerve activation and cyclooxygenase activity, consistent with absorption-mediated HCO3− secretion. These results suggest that absorption of luminal SCFA via SMCT1 and MCTs increases duodenal HCO3− secretion. In addition to SCFA sensing via free fatty acid receptors, the presence of rapid duodenal SCFA absorption may be important for the suppression of luminal bacterial colonization and implicated in the generation of functional dyspepsia due to bacterial overgrowth.

scholarly journals Keratin 8 absence down-regulates colonocyte HMGCS2 and modulates colonic ketogenesis and energy metabolism

2015 ◽  
Vol 26 (12) ◽  
pp. 2298-2310 ◽  
Author(s):  
Terhi O. Helenius ◽  
Julia O. Misiorek ◽  
Joel H. Nyström ◽  
Lina E. Fortelius ◽  
Aida Habtezion ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Mechanical Stability ◽  
Short Chain Fatty Acids ◽  
Monocarboxylate Transporter ◽  
Simple Type ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Intermediate Filament Proteins ◽  
Monocarboxylate Transporter 1 ◽  
Keratin 8

Simple-type epithelial keratins are intermediate filament proteins important for mechanical stability and stress protection. Keratin mutations predispose to human liver disorders, whereas their roles in intestinal diseases are unclear. Absence of keratin 8 (K8) in mice leads to colitis, decreased Na/Cl uptake, protein mistargeting, and longer crypts, suggesting that keratins contribute to intestinal homeostasis. We describe the rate-limiting enzyme of the ketogenic energy metabolism pathway, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), as a major down-regulated protein in the K8-knockout (K8−/−) colon. K8 absence leads to decreased quantity and activity of HMGCS2, and the down-regulation is not dependent on the inflammatory state, since HMGCS2 is not decreased in dextran sulfate sodium-induced colitis. Peroxisome proliferator–activated receptor α, a transcriptional activator of HMGCS2, is similarly down-regulated. Ketogenic conditions—starvation or ketogenic diet—increase K8+/+ HMGCS2, whereas this response is blunted in the K8−/− colon. Microbiota-produced short-chain fatty acids (SCFAs), substrates in the colonic ketone body pathway, are increased in stool, which correlates with decreased levels of their main transporter, monocarboxylate transporter 1 (MCT1). Microbial populations, including the main SCFA-butyrate producers in the colon, were not altered in the K8−/−. In summary, the regulation of the SCFA-MCT1-HMGCS2 axis is disrupted in K8−/− colonocytes, suggesting a role for keratins in colonocyte energy metabolism and homeostasis.

Regulation of butyrate uptake in Caco-2 cells by phorbol 12-myristate 13-acetate

2004 ◽  
Vol 286 (2) ◽  
pp. G197-G203 ◽  
Author(s):  
W. A. Alrefai ◽  
S. Tyagi ◽  
R. Gill ◽  
S. Saksena ◽  
C. Hadjiagapiou ◽  
...  
Keyword(s):  
Anion Exchange ◽  
Apical Membrane ◽  
Exchange Process ◽  
Maximum Velocity ◽  
Membrane Vesicles ◽  
Short Chain Fatty Acids ◽  
Monocarboxylate Transporter ◽  
Monocarboxylate Transporter 1 ◽  
Human Colonic Adenocarcinoma Cell ◽  
Colonic Lumen

Butyrate and the other short-chain fatty acids (SCFAs) are the most abundant anions in the colonic lumen. Also, butyrate is the preferred energy source for colonocytes and has been shown to regulate colonic electrolyte and fluid absorption. Previous studies from our group have demonstrated that the [Formula: see text] anion exchange process is one of the major mechanisms of butyrate transport across the purified human colonic apical membrane vesicles and the apical membrane of human colonic adenocarcinoma cell line Caco-2 and have suggested that it is mainly mediated via monocarboxylate transporter-1 (MCT-1) isoform. However, little is known regarding the regulation of SCFA transport by various hormones and signal transduction pathways. Therefore, the present studies were undertaken to examine whether hydrocortisone and phorbol 12-myristate 13-acetate (PMA) are involved in a possible regulation of the butyrate/anion exchange process in Caco-2 cells. The butyrate/anion exchange process was assessed by measuring a pH-driven [14C]butyrate uptake in Caco-2 cells. Our results demonstrated that 24-h incubation with PMA (1 μM) significantly increased [14C]butyrate uptake compared with incubation with 4αPMA (inactive form). In contrast, incubation with hydrocortisone had no significant effect on butyrate uptake in Caco-2 cells compared with vehicle (ethanol) alone. Induction of butyrate uptake by PMA appeared to be via an increase in the maximum velocity ( Vmax) of the transport process with no significant changes in the Kmof the transporter for butyrate. Parallel to the increase in the Vmaxof [14C]butyrate uptake, the MCT-1 protein level was also increased in response to PMA incubation. Our studies demonstrated that the butyrate/anion exchange was increased in response to PMA treatment along with the induction in the level of MCT-1 expression in Caco-2 cells.

Junction of the Epithelium and Lamina Propria of the Bovine Rumen Mucosa

1967 ◽  
Vol 25 ◽  
pp. 68-69
Author(s):  
Al W. Stinson
Keyword(s):  
Osmium Tetroxide ◽  
Squamous Epithelium ◽  
Short Chain Fatty Acids ◽  
Chloride Ions ◽  
Fermentation Products ◽  
Ruminant Species ◽  
Protective Shield ◽  
Stratified Squamous Epithelium ◽  
Lead Hydroxide ◽  
Acetic Acids

The stratified squamous epithelium which lines the ruminal compartment of the bovine stomach performs at least three important functions. (1) The upper keratinized layer forms a protective shield against the rough, fibrous, constantly moving ingesta. (2) It is an organ of absorption since a number of substances are absorbed directly through the epithelium. These include short chain fatty acids, potassium, sodium and chloride ions, water, and many others. (3) The cells of the deeper layers metabolize butyric acid and to a lesser extent propionic and acetic acids which are the fermentation products of rumen digestion. Because of the functional characteristics, this epithelium is important in the digestive process of ruminant species which convert large quantities of rough, fibrous feed into energy.Tissue used in this study was obtained by biopsy through a rumen fistula from clinically healthy, yearling holstein steers. The animals had been fed a typical diet of hay and grain and the ruminal papillae were fully developed. The tissue was immediately immersed in 1% osmium tetroxide buffered to a pH of 7.4 and fixed for 2 hrs. The tissue blocks were embedded in Vestapol-W, sectioned with a Porter-Blum microtome with glass knives and stained with lead hydroxide. The sections were studied with an RCA EMU 3F electron microscope.

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