Localization, function and regulation of the two intestinal fatty acid-binding protein types.
Although intestinal (I) and liver (L) fatty acid binding proteins (FABP) have been widely studied, the physiological significance of the presence of the two FABP forms (I- and L-FABP) in absorptive cells remains unknown as do the differences related to their distribution along the crypt-villus axis, regional expression, ontogeny and regulation in the human intestine. Our morphological experiments supported the expression of I- and L-FABP as early as 13 weeks of gestation. Whereas cytoplasmic immunofluorescence staining of L-FABP was barely detectable in the lower half of the villus and in the crypt epithelial cells, I-FABP was visualized in epithelial cells of the crypt-villus axis in all intestinal segments until the adult period in which the staining was maximized in the upper part of the villus. Immunoelectron microscopy revealed more intense labeling of L-FABP compared with I-FABP, accompanied with a heterogeneous distribution in the cytoplasm, microvilli and basolateral membranes. By western blot analysis, I- and L-FABP at 15 weeks of gestation appeared predominant in jejunum compared with duodenum, ileum, proximal and distal colon. Exploration of the maturation aspect documented a rise in L-FABP in adult tissues. Permanent transfections of Caco-2 cells with I-FABP cDNA resulted in decreased lipid export, apolipoprotein (apo) biogenesis and chylomicron secretion. Additionally, supplementation of Caco-2 with insulin, hydrocortisone and epidermal growth factor differentially modulated the expression of I- and L-FABP, apo B-48 and microsomal triglyceride transfer protein (MTP), emphasizing that these key proteins do not exhibit a parallel modulation. Overall, our findings indicate that the two FABPs display differences in localization, regulation and developmental pattern.
Levy
Emile
E
Department of Nutrition, CHU-Sainte-Justine, University of Montreal, 3175 Côte Ste-Catherine Road, Montreal, QC, H3T 1C5, Canada. emile.levy@recherche-ste-justine.qc.ca
Ménard
Daniel
D
Delvin
Edgard
E
Montoudis
Alain
A
Beaulieu
Jean-François
JF
Mailhot
Geneviève
G
Dubé
Nadia
N
Sinnett
Daniel
D
Seidman
Ernest
E
Bendayan
Moise
M
D018938:Caco-2 Cells; D003106:Colon / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007583:Jejunum / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D009928:Organ Specificity
C493319:FABP1 protein, human; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D008074:Lipoproteins