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Papers In Press, published online ahead of print August 3, 2001
Gastroenterology and Nutrition, Universite de Montreal, Montreal, Quebec H3T 1C5
Corresponding Author: levye{at}justine.umontreal.ca
Based on titration microcalorimetry and Caco-2 cell line transfection studies, it has been suggested that the Ala54Thr of FABP2 gene plays a significant role in the assimilation of dietary fatty acids. However, reports were divergent as to the in vivo interaction between this polymorphism and postprandial lipemia. We therefore determined the influence of this I-FABP polymorphism on intestinal fat transport using the human jejunal organ culture model, thus avoiding the interference of various circulating factors capable of metabolizing in vivo postprandial lipids. Analysis of DNA samples form 32 fetal intestines revealed 22 homozygotes for the wild-type Ala 54/Ala 54 genotype (0.69) and 10 heterozygotes for the polymorphic Thr 54/Ala 54 genotype (0.31). The Thr-encoding allele was associated with increased secretion of newly esterified triglycerides, augmented de novo apo B synthesis and elevated chylomicron output. On the other hand, no alterations were found in VLDL and HDL production, apo A-I biogenesis, as well as both microsomal triglyceride transfer protein mass and activity. Similarly, the alanine-to-threonine substitution at residue 54 did not result in changes in brush border hydrolytic activities (sucrase, glucoamylase, lactase, alkaline phosphatase), nor in glucose uptake or oxidation. Our data clearly document that the Ala 54 Thr polymorphism of FABP2 specifically influences small intestinal lipid absorption, without modifying glucose uptake or metabolism. It is proposed that, in the absence of confounding factors such as environmental and genetic variables, the FABP2 polymorphism has an important effect on postprandial lipids in vivo, potentially influencing plasma levels of lipids and atherogenesis.
J. Biol. Chem, 10.1074/jbc.M105713200
Submitted on June 20, 2001
Revised on August 2, 2001
Accepted on August 2, 2001
The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants
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