Monocarboxylate 4 mediated butyrate transport in a rat intestinal epithelial cell line
Abstract
Background Short chain fatty acids (SCFA) are absorbed by carrier mediated uptake in the small intestine by pH-dependent SCFA/HCO3 (-) exchangers on the apical membrane of epithelial cells. Conventional assumption is that MCT1 mediates SCFA/HCO3 (-) exchange in the intestine. Further, due to the presence of multiple such anion exchangers, the identity of the intestinal SCFA/HCO3 (-) has been controversial.Aims The aim of this study was to determine the identities of the butyrate transporter in the intestinal epithelial cells (IEC-18).Methods IEC-18 cells were treated with specific siRNAs for MCT1 and MCT4, and butyrate and lactate uptake studies were performed.Results Alpha-cyano-4-hydroxycinnamic acid inhibited lactate uptake but not butyrate uptake in IEC-18 cells, indicating that these two substrates are transported via two different transporter systems. MCT1 siRNA treatment abolished both MCT1 mRNA by more than 95 % and protein expression by 83 % as evidenced by RTQ-PCR and western blotting experiments. However, MCT1 siRNA treatment inhibited butyrate uptake upto 24 %, whereas it inhibited lactate uptake significantly by 70 %. Treatment with MCT4 siRNA inhibited MCT4 mRNA expression by 75 % and protein expression by 85 % in these cells. MCT4 siRNA inhibited butyrate uptake by 40 %. Further, several non-steroidal anti-inflammatory drugs (NSAIDs) are transported by the butyrate transporter. Finally, MCT4 siRNA inhibited salicylate uptake by 27 % indicating direct evidence for the transport of salicylate by MCT4.Conclusions These data indicate that MCT1 is the high affinity lactate transporter and MCT4 is the high affinity butyrate transporter in the intestinal epithelial cell line IEC-18.
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Abundant expression of monocarboxylate transporters in endothelial cells might facilitate crossing of the blood-brain barrier by short-chain fatty acids, since brain uptake of short-chain fatty acids has been demonstrated in rats following injection of 14C-SCFAs into the carotid artery.
“The abundant expression of MCTs in endothelial cells (75, 92) might facilitate crossing of the BBB by SCFAs since brain uptake of SCFAs has previously been demonstrated in rats following injection of 14C-SCFAs into the carotid artery (93).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [92]
SCFA receptors, mainly free fatty acid receptors and monocarboxylate transporters, have been discovered in the central and peripheral nervous systems, indicating direct signaling potential.
“Importantly, SCFA receptors, mainly free fatty acid receptors (349) and monocarboxylate transporters (350, 351), have been discovered in the central nervous system (CNS) and peripheral nervous system, indicating direct signaling potential.”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [351]
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PREBIOTICS FOR ACUTE ISCHEMIC STROKE
Renamastika, S. N., Wahyuningrum, D. R., PUTRI, V. A., & Aisy, R. (2021) · International Journal of Pharmacy and Pharmaceutical Sciences · doi:10.22159/ijpps.2021v13i5.41110 · Cited by 1 · see citing works
The role of short chain fatty acids in appetite regulation
Psichas, A. (2013) · doi:10.25560/23364
Is the Gut Microbiota an Organ?
Gamberi, C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-819265-8.00112-1
The impact of gut microbiome on neuro-autoimmune demyelinating diseases
Abolfazli, P., Nchama, C. N. A., & Lucke-Wold, B. P. (2024) · Academia Biology · doi:10.20935/acadbiol7397
- Authors
- Kekuda, R., Manoharan, P., Baseler, W., & Sundaram, U.
- Affiliations
- West Virginia University (US)
- Corresponding author
- Sundaram, Uma
- Venue
- Digestive Diseases and Sciences
- Published
- 2013-01-24
- Volume
- 58
- Issue
- 3
- Pages
- 660-667
- ISSN
- 0163-2116 (ISSN-L)
- 1573-2568
- OpenAlex
- W2126122559
- Cited by
- 68
- References
- 27
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 6 · 2013: 3
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Digestive Diseases and Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK‐067420, R01DK058034, DK-058034, R01DK067420)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- monocarboxylate transporters, MCT1, MCT4, short-chain fatty acids, lactate utilization, IEC-18 cells, intestinal epithelial cells, siRNA knockdown, HCCA
- MeSH terms
- Monocarboxylate Transport Protein 1, Animals, Anti-Inflammatory Agents, Non-Steroidal, Biological Transport, Butyrates, Cell Line, Epithelial Cells, Hydrogen-Ion Concentration, Intestinal Mucosa, Lactates, Muscle Proteins, RNA, Messenger, Substrate Specificity, Reverse Transcriptase Polymerase Chain Reaction, Salicylic Acid, Monocarboxylic Acid Transporters, Symporters, RNA Interference, Rats
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