An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance.

Abstract

The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population. A polymorphism at codon 54 of FABP2 was identified that results in an alanineencoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29). Pimas who were homozygous or heterozygous for the threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a lower mean insulin-stimulated glucose uptake rate, a higher mean insulin response to oral glucose and a mixed meal, and a higher mean fat oxidation rate compared with Pimas who were homozygous for the alanine-encoding allele. Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences. Titration microcalorimetry studies with purified recombinant protein showed that the threonine-containing protein had a twofold greater affinity for long-chain fatty acids than the alanine-containing protein. We conclude that the threonine-containing protein may increase absorption and/or processing of dietary fatty acids by the intestine and thereby increase fat oxidation, which has been shown to reduce insulin action. (J. Clin.

Two distinct types of fatty acid-binding protein are expressed in heart ventricle of Antarctic teleost fishes

“…Consequently, different FABPs may be needed among the tissues. With few exceptions [19][20][21], no significant difference in binding affinity has been found among FABP types or among fatty acids within a type [6,[22][23][24]. However, the rate of transfer of FABP-bound fatty acids to acceptor membranes varies greatly among types [25][26][27][28] and may reflect the functional diversity of FABPs.…”

The effect of FABP2 promoter haplotype on response to a diet with medium-chain triacylglycerols

“…It contains a single ligand binding site that has high affinity for saturated and unsaturated fatty acids (Baier et al 1995). FABP2 transports FA from the plasma membrane to the endoplasmic reticulum where the FA are esterified with glycerol-3-phosphate (G3P) to form triacylglycerols (TGs).…”

The Ala54Thr polymorphism in the fatty acid-binding protein 2 gene leads to higher food intake in Japanese women

“…5 A well-known single nucleotide polymorphism in the FABP2 gene, the missense Ala54Thr variation, is common in diverse populations. 6 Many, but not all, association studies on this variation in insulin resistance and fasting, or postprandial blood glucose and triglyceride levels have identified a relationship between genotypes and phenotypes.…”

“…Earlier studies have shown that FABP2-Thr has a greater binding affinity for long-chain fatty acids than FABP2-Ala, resulting in greater uptake of dietary fatty acids and a higher plasma lipid concentration. 5 Thr54 carriers also show higher lipid oxidation rates, which might prevent an excessive increase in fasting and postprandial lipids. 8 In the glucose-fatty acid cycle, enhanced lipid oxidation would impair glucose utilization, which might influence the blood glucose level and, consequently, food appetite.…”

“…In addition, there is a modulatory effect of emotion in the task with greater amygdala activation elicited during the viewing of fearful faces than the neutral ones. 5 All participants were genotyped for the 3 0 UTR indel (rs58575285) in the GRIK4 gene previously shown to be associated with bipolar disorder (Supplementary Methods). Eighteen subjects were carriers of the protective deletion (including one homozygote) whereas twenty-four subjects were homozygous for the insertion genotype.…”