The polymorphism at codon 54 of the FABP2 gene increases fat absorption inhuman intestinal explants

Based on titration microcalorimetry and Caco-2 cell line transfection studi es, it has been suggested that the A54T of the FABP2 gene plays a significa nt role in the assimilation of dietary fatty acids. However, reports were d ivergent with regard to the in vivo interaction between this polymorphism a nd postprandial lipemia. We therefore determined the influence of this inte stinal fatty acid-binding protein 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 postprandia l lipids. Analysis of DNA samples from 32 fetal intestines revealed 22 homo zygotes for the wild-type Ala-54/Ala-54 genotype (0.83) and 10 heterozygote s for the polymorphic Thr-54/Ala-54 genotype (0.17). The Thr-encoding allel e was associated with increased secretion of newly esterified triglycerides , augmented de novo apolipoprotein B synthesis, and elevated chylomicron ou tput. On the other hand, no alterations were found in very low density lipo protein and high density lipoprotein production, apolipoprotein A-I biogene sis, or microsomal triglyceride transfer protein mass and activity. Similar ly, the alanine to threonine substitution at residue 54 did not result in c hanges in brush border hydrolytic activities (sucrase, glucoamylase, lactas e, and alkaline phosphatase) or in glucose uptake or oxidation. Our data cl early document that the A54T polymorphism of FABP2 specifically influences small intestinal lipid absorption without modifying glucose uptake or metab olism. It is proposed that, in the absence of confounding factors such as e nvironmental and genetic variables, the FABP2 polymorphism has an important effect on postprandial lipids in vivo, potentially influencing plasma leve ls of lipids and atherogenesis.