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Significance of Short Chain Fatty Acid Transport by Members of the Monocarboxylate Transporter Family (MCT)

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Abstract

Metabolism of short-chain fatty acids (SCFA) in the brain, particularly that of acetate, appears to occur mainly in astrocytes. The differential use has been attributed to transport, but the extent to which transmembrane movement of SCFA is mediated by transporters has not been investigated systematically. Here we tested the possible contribution of monocarboxylate transporters to SCFA uptake by measuring fluxes with labelled compounds and by following changes of the intracellular pH in Xenopus laevis oocytes expressing the isoforms MCT1, MCT2 or MCT4. All isoforms mediated significant transport of acetate. Formate, however, was transported only by MCT1. The contribution of MCT1 to SCFA transport was determined by using phloretin as a high-affinity inhibitor, which allowed a paired comparison of oocytes with and without active MCT1.

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References

  1. Walter A, Gutknecht J (1984) Monocarboxylic acid permeation through lipid bilayer membranes. J Membr Biol 77:255–264

    Article  PubMed  CAS  Google Scholar 

  2. Alger JR, Prestegard JH (1979) Nuclear magnetic resonance study of acetic acid permeation of large unilamellar vesicle membranes. Biophys J 28:1–13

    Article  PubMed  CAS  Google Scholar 

  3. Klocke RA, Andersson KK, Rotman HH, Forster RE (1972) Permeability of human erythrocytes to ammonia and weak acids. Am J Physiol 222:1004–1013

    PubMed  CAS  Google Scholar 

  4. Sallee VL, Dietschy JM (1973) Determinants of intestinal mucosal uptake of short- and medium-chain fatty acids and alcohols. J Lipid Res 14:475–484

    PubMed  CAS  Google Scholar 

  5. Wolosin JM, Ginsburg H (1975) The permeation of organic acids through lecithin bilayers. Resemblance to diffusion in polymers. Biochim Biophys Acta 389:20–33

    Article  PubMed  CAS  Google Scholar 

  6. Wyss MT, Magistretti PJ, Buck A, Weber B (2011) Labeled acetate as a marker of astrocytic metabolism. J Cereb Blood Flow Metab 31:1668–1674

    Article  PubMed  CAS  Google Scholar 

  7. Muir D, Berl S, Clarke DD (1986) Acetate and fluoroacetate as possible markers for glial metabolism in vivo. Brain Res 380:336–340

    Article  PubMed  CAS  Google Scholar 

  8. Waniewski RA, Martin DL (1998) Preferential utilization of acetate by astrocytes is attributable to transport. J Neurosci 18:5225–5233

    PubMed  CAS  Google Scholar 

  9. Saleh AM, Rudnick H, Aronson PS (1996) Mechanism of H(+)-coupled formate transport in rabbit renal microvillus membranes. Am J Physiol 271:F401–F407

    PubMed  CAS  Google Scholar 

  10. Charney AN, Micic L, Egnor RW (1998) Nonionic diffusion of short-chain fatty acids across rat colon. Am J Physiol 274:G518–G524

    PubMed  CAS  Google Scholar 

  11. Ritzhaupt A, Ellis A, Hosie KB, Shirazi-Beechey SP (1998) The characterization of butyrate transport across pig and human colonic luminal membrane. J Physiol (Lond) 507:819–830

    Article  CAS  Google Scholar 

  12. Harig JM, Soergel KH, Barry JA, Ramaswamy K (1991) Transport of propionate by human ileal brush-border membrane vesicles. Am J Physiol 260:G776–G782

    PubMed  CAS  Google Scholar 

  13. Hadjiagapiou C, Schmidt L, Dudeja PK, Layden TJ, Ramaswamy K (2000) Mechanism(s) of butyrate transport in caco-2 cells: role of monocarboxylate transporter 1. Am J Physiol Gastrointest Liver Physiol 279:G775–G780

    PubMed  CAS  Google Scholar 

  14. Stein J, Zores M, Schroder O (2000) Short-chain fatty acid (SCFA) uptake into Caco-2 cells by a pH-dependent and carrier mediated transport mechanism. Eur J Nutr 39:121–125

    Article  PubMed  CAS  Google Scholar 

  15. Halestrap AP, Price NT (1999) The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 343(Pt 2):281–299

    Article  PubMed  CAS  Google Scholar 

  16. Broer S, Schneider HP, Broer A, Rahman B, Hamprecht B, Deitmer JW (1998) Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem J 333:167–174

    PubMed  CAS  Google Scholar 

  17. Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW (1999) Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J 341:529–535

    Article  PubMed  CAS  Google Scholar 

  18. Dimmer KS, Friedrich B, Lang F, Deitmer JW, Broer S (2000) The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochem J 350:219–227

    Article  PubMed  CAS  Google Scholar 

  19. Grollman EF, Philp NJ, McPhie P, Ward RD, Sauer B (2000) Determination of transport kinetics of chick MCT3 monocarboxylate transporter from retinal pigment epithelium by expression in genetically modified yeast. Biochemistry 39:9351–9357

    Article  PubMed  CAS  Google Scholar 

  20. Manning Fox JE, Meredith D, Halestrap AP (2000) Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. J Physiol 529(Pt 2):285–293

    PubMed  CAS  Google Scholar 

  21. Poole RC, Halestrap AP, Price SJ, Levi AJ (1989) The kinetics of transport of lactate and pyruvate into isolated cardiac myocytes from guinea pig. Kinetic evidence for the presence of a carrier distinct from that in erythrocytes and hepatocytes. Biochem J 264:409–418

    PubMed  CAS  Google Scholar 

  22. Poitry-Yamate CL, Poitry S, Tsacopoulos M (1995) Lactate released by Muller glial cells is metabolized by photoreceptors from mammalian retina. J Neurosci 15:5179–5191

    PubMed  CAS  Google Scholar 

  23. Pellerin L (2003) Lactate as a pivotal element in neuron-glia metabolic cooperation. Neurochem Int 43:331–338

    Article  PubMed  CAS  Google Scholar 

  24. Pellerin L, Bergersen LH, Halestrap AP, Pierre K (2005) Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain. J Neurosci Res 79:55–64

    Article  PubMed  CAS  Google Scholar 

  25. Whitaker-Menezes D, Martinez-Outschoorn UE, Lin Z, Ertel A, Flomenberg N, Witkiewicz AK, Birbe RC, Howell A, Pavlides S, Gandara R, Pestell RG, Sotgia F, Philp NJ, Lisanti MP (2011) Evidence for a stromal-epithelial “lactate shuttle” in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts. Cell Cycle 10:1772–1783

    Article  PubMed  CAS  Google Scholar 

  26. Martin PM, Gopal E, Ananth S, Zhuang L, Itagaki S, Prasad BM, Smith SB, Prasad PD, Ganapathy V (2006) Identity of SMCT1 (SLC5A8) as a neuron-specific Na + -coupled transporter for active uptake of L-lactate and ketone bodies in the brain. J Neurochem 98:279–288

    Article  PubMed  CAS  Google Scholar 

  27. Carpenter L, Halestrap AP (1994) The kinetics, substrate and inhibitor specificity of the lactate transporter of Ehrlich-Lettre tumour cells studied with the intracellular pH indicator BCECF. Biochem J 304:751–760

    PubMed  CAS  Google Scholar 

  28. Broer S, Rahman B, Pellegri G, Pellerin L, Martin JL, Verleysdonk S, Hamprecht B, Magistretti PJ (1997) Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons. J Biol Chem 272:30096–30102

    Article  PubMed  CAS  Google Scholar 

  29. Wagner CA, Friedrich B, Setiawan I, Lang F, Broer S (2000) The use of Xenopus laevis oocytes for the functional characterization of heterologously expressed membrane proteins. Cell Physiol Biochem 10:1–12

    Article  PubMed  CAS  Google Scholar 

  30. Becker HM, Broer S, Deitmer JW (2004) Facilitated lactate transport by MCT1 when coexpressed with the sodium bicarbonate cotransporter (NBC) in xenopus oocytes. Biophys J 86:235–247

    Article  PubMed  CAS  Google Scholar 

  31. Tosco M, Orsenigo MN, Gastaldi G, Faelli A (2000) An endogenous monocarboxylate transport in Xenopus laevis oocytes. Am J Physiol Regul Integr Comp Physiol 278:R1190–R1195

    PubMed  CAS  Google Scholar 

  32. Deuticke B (1982) Monocarboxylate transport in erythrocytes. J Membr Biol 70:89–103

    Article  PubMed  CAS  Google Scholar 

  33. Poole RC, Halestrap AP (1993) Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am J Physiol 264:C761–C782

    PubMed  CAS  Google Scholar 

  34. Miyauchi S, Gopal E, Fei YJ, Ganapathy V (2004) Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. J Biol Chem 279:13293–13296

    Article  PubMed  CAS  Google Scholar 

  35. Broer S (2010) Xenopus laevis oocytes. Methods Mol Biol 637:295–310

    Article  PubMed  CAS  Google Scholar 

  36. Dienel GA, Liu K, Cruz NF (2001) Local uptake of (14)C-labeled acetate and butyrate in rat brain in vivo during spreading cortical depression. J Neurosci Res 66:812–820

    Article  PubMed  CAS  Google Scholar 

  37. Nedergaard M, Goldman SA (1993) Carrier-mediated transport of lactic acid in cultured neurons and astrocytes. Am J Physiol 265:R282–R289

    PubMed  CAS  Google Scholar 

  38. Edmond J, Robbins RA, Bergstrom JD, Cole RA, de Vellis J (1987) Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J Neurosci Res 18:551–561

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Stefan Bröer.

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Special Issue: In Honor of Leif Hertz.

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Moschen, I., Bröer, A., Galić, S. et al. Significance of Short Chain Fatty Acid Transport by Members of the Monocarboxylate Transporter Family (MCT). Neurochem Res 37, 2562–2568 (2012). https://doi.org/10.1007/s11064-012-0857-3

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  • DOI: https://doi.org/10.1007/s11064-012-0857-3

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