Abstract
We investigated, for the first time, the expression of I- and L-FABP in two very rare hereditary lipid malabsorption syndromes as compared with normal subjects. Abetalipoproteinemia (ABL) and Anderson’s disease (AD) are characterized by an inability to export alimentary lipids as chylomicrons that result in fat loading of enterocytes. Duodeno-jejunal biopsies were obtained from 14 fasted normal subjects, and from four patients with ABL and from six with AD. Intestinal FABP expression was investigated by immuno-histochemistry, western blot, ELISA and Northern blot analysis. In contrast to normal subjects, the cellular immunostaining for both FABPs was clearly decreased in patients, as the enterocytes became fat-laden. In patients with ABL, the intestinal contents of I- (60.7 ± 13.38 ng/mg protein) and L-FABP (750.3 ± 121.3 ng/mg protein) are significantly reduced (50 and 35%, P < 0.05, respectively) as compared to normal subjects (I-135.3 ± 11.1 ng, L-1211 ± 110 ng/mg protein). In AD, the patients also exhibited decreased expression (50%, P < 0.05; I-59 ± 11.88 ng, L-618.2 ± 104.6 ng/mg protein). Decreased FABP expression was not associated with decreased mRNA levels. The results suggest that enterocytes might regulate intracellular FABP content in response to intracellular fatty acids, which we speculate may act as lipid sensors to prevent their intracellular transport.
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Abdelwahab SA, Owada Y, Kitanaka N, Iwasa H, Sakagami H, Kondo H (2003) Localization of brain-type fatty acid-binding protein in Kupffer cells of mice and its transient decrease in response to lipopolysaccharide. Histochem Cell Biol 119:469–475
Agellon LB, Toth MJ, Thomson AB (2002) Intracellular lipid binding proteins of the small intestine. Mol Cell Biochem 239:79–82
Aguglia U, Annesi G, Pasquinelli G, Spadafora P, Gambardella A, AnnesiF, Pasqua AA, Cavalcanti F, Crescibene L, Bagala A, Bono F, Oliveri RL, Valentino P, Zappia M, Quattrone A (2000) Vitamin E deficiency due to chylomicron retention disease in Marinesco-Sjögren syndrome. Ann Neuro 47:260–264
Alpers DH, Bass NM, Engle MJ, DeSchryver-Kecskemeti K (2000) Intestinal fatty acid binding protein may favor differential apical fatty acid binding in the intestine. Biochim Biophys Acta 1483:352–362
Alpers DH, Strauss AW, Ockner RK, Bass NM, Gordon JI (1984) Cloning of a cDNA encoding rat intestinal fatty acid binding protein. Proc Natl Acad Sci USA 81:313–317
Bass NM, Manning JA, Ockner RK, Gordon JI, Seetharam S, Alpers DH (1985) Regulation of the biosynthesis of two distinct fatty acid-binding proteins in rat liver and intestine. Influences of sex difference and of clofibrate. J Biol Chem 260:1432–1436
Berriot-Varoqueaux N, Aggerbeck LP, Samson-Bouma ME, Wetterau JR (2000) The role of the microsomal triglyceride transfer protein in abetalipoproteinemia. Annu Rev Nutr 20:663–697
Berriot-Varoqueaux N, Dannoura AH, Moreau A, Verthier N, Sassolas A, Cadiot G, Lachaux A, Munck A, Schmitz J, Aggerbeck LP, Samson-Bouma ME (2001) Apoliprotein B48 glycosylation in Abetalipoproteinemia and Anderson’s disease. Gastroenterology 121:1101–1108
Besnard P, Foucaud L, Mallordy A, Berges C, Kaikaus RM, Bernard A, Bass NM, Carlier H (1995) Expression of fatty acid binding protein in the liver during pregnancy and lactation in the rat. Biochim Biophys Acta 1258:153–158
Besnard P, Niot I, Poirier H, Clement L, Bernard A (2002) New insights into the fatty acid-binding protein (FABP) family in the small intestine. Mol Cell Biochem 239:139–147
Bouma ME, Beucler I, Aggerbeck LP, Infante R, Schmitz J (1986) Hypobetalipoproteinemia with accumulation of an apoprotein B-like protein in intestinal cells. J Clin Invest 78:398–410
Bouma ME, Beucler I, Pessah M, Heinzmann C, Lusis AJ, Naim HY, Ducastelle T, Leluyer B, Schmitz J, Infante R, Aggerbeck LP(1990) Description of two different patients with abetalipoproteinemia: synthesis of a normal-sized apolipoprotein B-48 in intestinal organ culture. J Lipid Res 31:1–15
Dannoura AH, Berriot-Varoqueaux N, Amati P, Abadie V, Verthier N, Schmitz J, Wetterau JR, Samson-Bouma ME, Aggerbeck LP (1999). Anderson’s disease: exclusion of apolipoprotein and intracellular lipid transport genes. Arterioscler Thromb Vasc Biol 19:2494–2508
Dube N, Delvin E, Yotov W, Garofalo C, Bendayan M, Veerkamp JH, Levy E (2001) Modulation of intestinal and liver fatty acid-binding proteins in Caco-2 cells by lipids, hormones and cytokines. J Cell Biochem 81:613–620
Duluc I, Jost B, Freund JN (1993) Multiple levels of control of the stage- and region-specific expression of rat intestinal lactase. J Cell Biol 123:1577–1586
Foucaud L, Niot I, Kanda T, Besnard P (1998) Indirect dexamethasone down-regulation of the liver fatty acid-binding protein expression in rat liver. Biochim Biophys Acta 1391:204–212
Glatz JF, Luiken JJ, van Bilsen M, van der Vusse GJ (2002) Cellular lipid binding proteins as facilitators and regulators of lipid metabolism. Mol Cell Biochem 239:3–7
Gordon JI, Alpers DH, Ockner RK, Strauss AW (1983) The nucleotide sequence of rat liver fatty acid binding protein mRNA. J Biol Chem 258:3356–3363
Green PHR, Lefkowitch JH, Glickman RM, Riley JW, Blum CB (1982) Apolipoprotein localization and quantitation in the human intestine. Gastroenterology 83:1223–1230
Guthmann F, Borchers T, Wolfrum C, Wustrack T, Bartholomaus S, Spener F (2002) Plasma concentration of intestinal- and liver-FABP in neonates suffering from necrotizing enterocolitis and in healthy preterm neonates. Mol Cell Biochem 239:227–234
Hussain MM, Fatma S, Pan X, Iqbal J (2005) Intestinal lipoprotein assembly. Curr Opin Lipidol 16:281–285
Jones B, Jones EL, Bonney SA, Patel HN, Mensenkamp AR, Eichenbaum-Voline S, Rudling M, Myrdal U, Annesi G, Naik S, Meadows N, Quattrone A, Islam SA, Naoumova RP, Angelin B, Infante R, Levy E, Roy CC, Freemont PS, Scott J, Shoulders CC (2003) Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders. Nat Genet 34:29–31
Kanda T, Fujii H, Fujita M, Sakai Y, Ono T, Hatakeyama K (1995) Intestinal fatty acid binding protein is available for diagnosis of intestinal ischaemia: immunochemical analysis of two patients with ischaemic intestinal diseases. Gut 36:788–791
Le Beyec J, Delers F, Jourdant F, Schreider C, Chambaz J, Cardot P, Pincon-Raymond M (1997) A complete epithelial organization of Caco-2 cells induces I-FABP and potentializes apolipoprotein gene expression. Exp Cell Res 236:311–320
Levy E, Chouraqui JP, Roy CC (1988) Steatorrhea and disorders of chylomicron synthesis and secretion. Pediatr Clin North Am 35:53–67
Maiuri L, Rossi M, Raia V, Garipoli V, Hughes LA, Swallow D, Noren O, Sjostrom H, Auricchio S (1994) Mosaic regulation of lactase in human adult-type hypolactasia. Gastroenterology 107:54–60
Mallordy A, Poirier H, Besnard P, Niot I, Carlier H (1995) Evidence for transcriptional induction of the liver fatty-acid-binding-protein gene by bezafibrate in the small intestine. Eur J Biochem 227:801–807
Montoudis A, Delvin E, Menard D, Beaulieu JF, Jean D, Tremblay E, Bendayan M, Levy E (2006) Intestinal-fatty acid binding protein and lipid transport in human intestinal epithelial cells. Biochem Biophys Res Commun 339:248–254
Newberry EP, Xie Y, Kennedy S, Han X, Buhman KK, Luo J, Gross RW, Davidson NO (2003) Decreased hepatic triglyceride accumulation and altered fatty acid uptake in mice with deletion of the liver fatty acid-binding protein gene. J Biol Chem 278:51664–51672
Ockner RK, Manning JA (1974) Fatty acid binding protein in small intestine. Identification, isolation and evidence for its role in cellular fatty acid transport. J Clin Invest 54:326–338
Pelsers MM, Namiot Z, Kisielewski W, Namiot A, Januszkiewicz M, Hermens WT, Glatz JF (2003) Intestinal-type and liver-type fatty acid-binding protein in the intestine. Tissue distribution and clinical utility. Clin Biochem 36:529–535
Pelsers MM, Hermens WT, Glatz JF (2005) Fatty acid-binding proteins as plasma markers of tissue injury. Clin Chim Acta 352:15–35
Poirier H, Niot I, Degrace P, Monnot MC, Bernard A, Besnard P (1997) Fatty acid regulation of fatty acid-binding protein expression in the small intestine. Am J Physiol 273:G289–G295
Rehberg EF, Samson-Bouma ME, Kienzle B, Blinderman L, Jamil H, Wetterau JR, Aggerbeck LP, Gordon DA (1996) A novel abetalipoproteinemia genotype. J Biol Chem 271:29945–29952
Sharp D, Blinderman L, Combs KA, Kienzle B, Ricci B, Wager-Smith K, Gil CM, Turck CW, Bouma ME, Rader DJ, Aggerbeck LP, Gregg RE, Gordon DA, Wetterau JR (1993) Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinemia. Nature 365:65–69
Shields HM, Bates ML, Bass NM, Best CJ, Alpers DH, Ockner RK (1986) Light microscopic immunocytochemical localization of hepatic and intestinal types of fatty acid-binding proteins in rat intestine. J Lipid Res 27:549–557
Shoulders CC, Brett DJ, Bayliss JD, Narcisi TME, Jarmuz A, Grantham TT, Leoni PRD, Bhattacharya S, Pease RJ, Cullen PM, Levi S, Byfield PGH, Purkiss P, Scott J (1993) Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein. Hum Mol Gen 2:2109–2116
Storch J, Thumser AE (2000) The fatty acid transport function of fatty acid-binding proteins. Biochim Biophys Acta 1486:28–44
Thumser AE, Storch J (2000) Liver and intestinal fatty acid-binding proteins obtain fatty acids from phospholipid membranes by different mechanisms. J Lipid Res 41:647–656
Vassileva G, Huwyler L, Poirier K, Agellon LB, Toth MJ (2000) The intestinal fatty acid binding protein is not essential for dietary fat absorption in mice. Faseb J 14:2040–2046
Wang AB, Liu DP, Liang CC (2003) Regulation of human apolipoprotein B gene expression at multiple levels. Exp Cell Res 290:1–12
Ways PO, Parmentier CM, Kayden HJ, Jones JW, Saunders DR, Rubin CE (1967) Studies on the absorptive defect for triglyceride in abetalipoproteinemia. J Clin Invest 46:35–46
Wetterau JR, Aggerbeck LP, Bouma ME, Eisenberg C, Munck A, Hermier M, Schmitz J, Gay G, Rader DJ, Gregg RE (1992) Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science 258:999–1001
Wong MH, Saam JR, Stappenbeck TS, Rexer CH, Gordon JI (2000) Genetic mosaic analysis based on Cre recombinase and navigated laser capture microdissection. Proc Natl Acad Sci USA 97:12601–12606
Woudstra TD, Drozdowski LA, Wild GE, Clandinin MT, Agellon LB, Thomson AB (2004) The age-related decline in intestinal lipid uptake is associated with a reduced abundance of fatty acid-binding protein. Lipids 39:603–610
Acknowledgments
This study was supported financially by the Institute National de la Santé et de la Recherche Médicale (INSERM) and by funds from GlaxoSmithKline (USA) and Conseil Régional de Bourgogne (France). We also thank Pr. A Lachaux (Département de Pédiatrie, Hôpital E. Herriot, Lyon, France), Pr. J. Schmitz (Département de Pédiatrie, Hôpital Necker-Enfants Malades, 75015 Paris), Pr. JP Cézard (Service de Gastroentérologie et Nutrition Pédiatrique, Hôpital R. Debré, Paris), Dr. P. Crenn and Dr. T. Aparicio (Service de Gastroentérologie, Hôpital Bichat-C. Bernard, 75018 Paris), Dr. F. Walker (Service d’Anatomopathologie Hôpital Bichat-C. Bernard, 75018 Paris), and D. Cazal (Service d’Anatomie Pathologique, Hôpital Beaujon, 92118 Clichy) for referring to us their patients and O Thibaudeau for excellent technical assistance (IFR02, Intitut C Bernard-Physiologie et Pathologie, Faculté de Médecine X. Bichat, 75018 Paris). The authors would like to thank Mrs. T. Lehy and Pr A. Raisonnier for very helpful discussions.
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Guilmeau, S., Niot, I., Laigneau, J.P. et al. Decreased expression of Intestinal I- and L-FABP levels in rare human genetic lipid malabsorption syndromes. Histochem Cell Biol 128, 115–123 (2007). https://doi.org/10.1007/s00418-007-0302-x
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DOI: https://doi.org/10.1007/s00418-007-0302-x