Abstract
Leptin is secreted by gastric mucosa and is able to reach the intestinal lumen where its receptors are located in the apical membrane of the enterocytes. We have previously demonstrated that apical leptin inhibits sugar and amino acids uptake in vitro and glucose absorption in vivo. Since leptin receptors are also expressed in the basolateral membrane of the enterocytes, the aim of the present work was to investigate whether leptin acting from the basolateral side could also regulate amino acid uptake. Tritiated Gln and β-Ala were used to measure uptake into Caco-2 cells grown on filters, in the presence of basal leptin at short incubation times (5 and 30 min) and after 6 h of preincubation with the hormone. In order to compare apical and basal leptin effect, Gln and β-Ala uptake was measured in the presence of leptin acting from the apical membrane also in cells grown on filters. Basal leptin (8 mM) inhibited by ~15–30 % the uptake of 0.1 mM Gln and 1 mM β-Ala quickly, after 5 min exposure, and the effect was maintained after long preincubation periods. Apical leptin had the same effect. Moreover, the inhibition was rapidly and completely reversed when leptin was removed from the apical or basolateral medium. These results extend our previous findings and contribute to the vision of leptin as an important hormonal signal for the regulation of intestinal absorption of nutrients.
Similar content being viewed by others
References
Bado A, Levasseur S, Attoub S, Kermorgant S, Laigneau JP, Bortoluzzi MN, Moizo L, Lehy T, Guerre-Millo M, Le Marchand-Bruste Y, Lewin MJ (1998) The stomach is a source of leptin. Nature 394:790–793
Barrenetxe J, Barber A, Lostao MP (2001) Leptin effect on galactose absorption in mice jejunum. J Physiol Biochem 57:345–346
Barrenetxe J, Villaro AC, Guembe L, Pascual I, Munoz-Navas M, Barber A, Lostao MP (2002) Distribution of the long leptin receptor isoform in brush border, basolateral membrane, and cytoplasm of enterocytes. Gut 50:797–802
Buyse M, Berlioz F, Guilmeau S, Tsocas A, Voisin T, Peranzi G, Merlin D, Laburthe M, Lewin MJ, Roze C, Bado A (2001) PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine. J Clin Invest 108:1483–1494
Buyse M, Sitaraman SV, Liu X, Bado A, Merlin D (2002) Luminal leptin enhances CD147/MCT-1-mediated uptake of butyrate in the human intestinal cell line Caco2-BBE. J Biol Chem 277:28182–28190
Cammisotto PG, Renaud C, Gingras D, Delvin E, Levy E, Bendayan M (2005) Endocrine and exocrine secretion of leptin by the gastric mucosa. J Histochem Cytochem 53:851–860
Cammisotto PG, Bendayan M (2012) A review on gastric leptin: the exocrine secretion of a gastric hormone. Anat Cell Biol 45:1–16
Cammisotto PG, Bendayan M, Levy E (2012) Regulation of leptin receptor expression in human polarized Caco-2/15 cells. Endocr Metab Immune Disord Drug Targets 12:57–70
Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P (1995) Recombinat mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 296:546–549
De Matteis R, Dashtipour K, Ognibene A, Cinti S (1998) Localization of leptin receptor splice variants in mouse peripheral tissues by immunohistochemistry. Proc Nutr Soc 57:441–448
Ducroc R, Guilmeau S, Akasbi K, Devaud H, Buyse M, Bado A (2005) Luminal leptin induces rapid inhibition of active intestinal absorption of glucose mediated by sodium-glucose cotransporter 1. Diabetes 54:348–354
Ducroc R, Sakar Y, Fanjul C, Barber A, Bado A, Lostao MP (2010) Luminal leptin inhibits L-glutamine transport in rat small intestine: involvement of ASCT2 and B0AT1. Am J Physiol Gastrointest Liver Physiol 299:179–185
Fanjul C, Barrenetxe J, Iñigo C, Sakar Y, Ducroc R, Barber A, Lostao MP (2012) Leptin regulates sugar and amino acids transport in the human intestinal cell line Caco-2. Acta Physiol 205:82–91
Gertler A (2009) Leptin and leptin antagonists, Landes Bioscience
Gómez JM, Molina A, Fernández-Castañer M, Casamitjana R, Martínez-Matos JA, Soler J (1999) Insulin regulation of leptin synthesis and secretion in humans: the model of myotonic dystrophy. Clin Endocrinol 50:569–575
Halbleib JM, Saaf AM, Brown PO, Nelson WJ (2007) Transcriptional modulation of genes encoding structural characteristics of differentiating enterocytes during development of a polarized epithelium in vitro. Mol Bio Cell 18:4261–4278
Heinonen MV, Purhonen AK, Miettinen P, Pääkkönen M, Pirinen E, Alhava E, Akerman K, Herzig KH (2005) Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding. Regul Pept 130:7–13
Iñigo C, Barber A, Lostao MP (2004) Leptin effect on intestinal galactose absorption in ob/ob and db/db mice. J Physiol Biochem 60:93–97
Iñigo C, Patel N, Kellett GL, Barber A, Lostao MP (2007) Luminal leptin inhibits intestinal sugar absorption in vivo. Acta Physiol 190:303–310
Lostao MP, Urdaneta E, Martinez-Anso E, Barber A, Martinez JA (1998) Presence of leptin receptors in rat small intestine and leptin effect on sugar absorption. FEBS Lett 423:302–306
Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S et al (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1:1155–1161
Margetic S, Gazzola C, Pegg GG, Hill RA (2002) Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 26:1407–1433
Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 259:540–543
Sakar Y, Nazaret C, Letteron P, Ait Omar A, Avenati M, Viollet B, Ducroc R, Bado A (2009) Positive regulatory control loop between gut leptin and intestinal GLUT2/GLUT5 transporters links to hepatic metabolic functions in rodents. PLoS One 4:e7935
Stan S, Levy E, Bendayan M, Zoltowska M, Lambert M, Michaud J, Asselin C, Delvin EE (2001) Effect of human recombinant leptin on lipid handling by fully differentiated Caco-2 cells. FEBS Lett 508:80–84
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432
Acknowledgments
We thank Asunción Redín for its unconditional technical assistance and Ana Barber for her helpful comments. This work was supported by “Ministerio de Educación y Ciencia,” Spain (Grant BFU 2007 60420/BFI) and “Fundación Marcelino Botín.” The Spanish group is member of the Network for Cooperative Research on Membrane Transport Proteins (REIT), co-funded by the “Ministerio de Educación y Ciencia,” Spain and the European Regional Development Fund (ERDF) (Grant BFU2007-30688-E/BFI). C. Fanjul is a recipient of a predoctoral fellowship from “Asociación de Amigos,” University of Navarra.
Conflict of interest
No conflicts of interest, financial, or otherwise are declared by the authors.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fanjul, C., Barrenetxe, J. & Lostao, M.P. Basal leptin regulates amino acid uptake in polarized Caco-2 cells. J Physiol Biochem 69, 507–512 (2013). https://doi.org/10.1007/s13105-013-0239-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13105-013-0239-6