The Polymorphism at Codon 54 of the FABP2 Gene Increases Fat Absorption in Human Intestinal Explants

Abstract

Based on titration microcalorimetry and Caco-2 cell line transfection studies, it has been suggested that the A54T of the FABP2 gene plays a significant role in the assimilation of dietary fatty acids. However, reports were divergent with regard to the in vivo interaction between this polymorphism and postprandial lipemia. We therefore determined the influence of this intestinal 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 postprandial lipids. Analysis of DNA samples from 32 fetal intestines revealed 22 homozygotes for the wild-type Ala-54/ Ala-54 genotype (0.83) and 10 heterozygotes for the polymorphic Thr-54/Ala-54 genotype (0.17). The Thr-encoding allele was associated with increased secretion of newly esterified triglycerides, augmented de novo apolipoprotein B synthesis, and elevated chylomicron output. On the other hand, no alterations were found in very low density lipoprotein and high density lipoprotein production, apolipoprotein A-I biogenesis, or 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, and alkaline phosphatase) or in glucose uptake or oxidation. Our data clearly document that the A54T 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.

Overproduction of intestinal lipoprotein containing apolipoprotein B-48 in Psammomys obesus: impact of dietary n-3 fatty acids

“…An amount of medium (0.8 ml) sufficient to dampen the lens paper was added. Explants were cultured in serum-free Leibovitz L-15 medium according to the technique described previously [27,28]. After a 30-min stabilisation period, the medium was replaced with fresh medium containing a final amount of 1.0 μmol/ml unlabelled oleic acid with 0.018 MBq [ 14 C]-oleic acid (specific activity, 2.11 GBq/mmol; GE Healthcare Bio-Sciences, Baie D'Urfé, QC, Canada) in a micellar mixture (6.6 mmol/l sodium taurocholate, 1 mmol/l oleic acid, 0.5 mmol/l monoolein, 0.1 mmol/l cholesterol, and 0.6 mmol/l phosphatidylcholine) [29].…”

“…Quenching was corrected using computerised curves generated with external standards. An aliquot of the tissue homogenate was used for protein determinations [27][28][29][30]. For the determination of secreted lipoproteins, the medium supplemented with anti-proteases was first mixed with a plasma lipid carrier (2:0.6 vol/vol) to efficiently isolate the newly synthesised triglyceride-rich lipoproteins.…”

“…For the determination of secreted lipoproteins, the medium supplemented with anti-proteases was first mixed with a plasma lipid carrier (2:0.6 vol/vol) to efficiently isolate the newly synthesised triglyceride-rich lipoproteins. The latter were then isolated at a density of 1.006 g/ml by spinning at 100,000 g for 2.26 h with a tabletop ultracentrifuge (Beckman Instruments) as described previously [27,28].…”

“…To provide a carrier for lipoproteins synthesised in vitro, postprandial plasma was obtained from healthy volunteers 3 h after the ingestion of fat (50 g/1.73 m 2 ) as described previously [27,28].…”

Avancées dans la dissection fonctionnelle du transport intestinal des lipides

“…Comme l'a démontré notre récente étude, les enfants et adolescents exhibant un polymorphisme de I-FABP (se traduisant par une substitution de l'alanine par la thréonine à la position 54) présentent de plus grands risques d'être atteints de maladie cardiovasculaire [27]. En culture, des explants intestinaux indiquent également une capacité supérieure de la variante Ala54Thr du I-FABP à synthétiser les lipides et à produire les CM [28], ce qui avantagerait la consommation des AG par les organes périphériques aux dépens des glucides, faisant ainsi grimper les niveaux de glycémie et, par là, la résistance à l'insuline. .…”