Disease relevance of Fabp2

• We discovered that Fabpi-/- mice are viable, but they display alterations in body weight and are hyperinsulinemic [1].
• To explore a possible cause for this gender dimorphic effect, we examined the changes in expression of genes that encode liver fatty acid binding protein (L-FABP) and ileal lipid binding protein in the small intestine resulting from I-FABP deficiency [2].

High impact information on Fabp2

• We have used an intestine-specific fatty acid binding protein gene, Fabpi, as a model for studying regulation of gene expression in this unique developmental system [3].
• They encode three homologous small cytoplasmic hydrophobic ligand binding proteins--liver fatty acid binding protein (L-FABP), intestinal fatty acid binding protein (I-FABP), and cellular retinol binding protein II (CRBP II)--and two apolipoproteins--apoAI and apoAIV [4].
• Male Fabpi-/- mice had elevated plasma triacylglycerols and weighed more regardless of the dietary fat content [1].
• The intestinal fatty acid binding protein (I-FABP) belongs to a family of 15 kDa clamshell-like proteins that are found in many different tissues [1].
• We propose that I-FABP functions as a lipid-sensing component of energy homeostasis that alters body weight gain in a gender-specific fashion [1].

Biological context of Fabp2

• We have isolated the mouse I-FABP gene (Fabpi) and determined its nucleotide sequence [5].
• There was no discernible alteration of overall morphology or histology in the small intestine but changes in liver histology were evident in I-FABP deficient male mice [2].
• The zebrafish I-FABP cDNA hybridized to single restriction fragments of total zebrafish genomic DNA digested with the restriction endonucleases PstI Bg/II or EcoRI suggesting that a single copy of the I-FABP gene is present in the zebrafish genome [6].
• Double-label immunofluorescent analyses using L-FABP and I-FABP antibodies indicated that on the 18th day of gestation the proximal small intestinal columnar epithelium contains several populations of enterocytes expressing neither, one, or both proteins [4].
• The onset and resolution of this mosaicism varies between I-FABP, L-FABP, and CRBP II in the proximal small bowel, although it completely resolves by the first postnatal day [4].

Anatomical context of Fabp2

• In addition, Fabpi expression in enterocytes was examined as a function of their differentiation along the crypto-to-villus and duodenal-to-colonic axes of the small intestine [5].
• The rat intestinal fatty acid binding protein (I-FABP) gene has been used as a model to study temporal and spatial differentiation of the gut epithelium while its protein product has been used as a model for examining the atomic details of noncovalent fatty acid-protein interactions [5].
• SV40 large T antigen (TAg(Wt)) or a mutant derivative (TAg(K107/8)) that does not bind pRB was expressed in small intestinal villus enterocytes under the control of elements from the intestinal fatty acid binding protein gene (Fabpi) [7].
• However, other I-FABP/hGH fusion genes that exhibit differentiation-dependent changes in their expression along the crypt-to-villus axis do not manifest the same pattern of differentiation-dependent change in activity in this cell line [8].
• We have compared and contrasted the transcriptional activity of four fusion genes composed of elements from the 5'-nontranscribed domain of rat Fabpi linked to the human growth hormone gene (I-FABP/hGH) in transgenic mice and in five primate epithelial cell lines derived from intestine, liver, kidney, and cervix [8].

Associations of Fabp2 with chemical compounds

• Finally, predictions of the structure of mouse I-FABP using the refined 2.0 A model of rat I-FABP, suggest that a proline found at position 69 of the mouse, but not rat, protein may affect its ligand binding properties [5].
• I-FABP deficiency had no effect on glucose tolerance in male mice but it appeared to be improved in female mice [2].
• Surprisingly, both L- and I-FABP expression increased ethanolamine plasmalogen mass 1.6- and 1.1-fold, respectively, while choline plasmalogen mass was increased 2.3- and 1.7-fold, respectively [9].
• In contrast, I-FABP expression only increased the masses of ChoGpl and PtdSer, 1.2- and 3.1-fold, respectively [9].
• Although, the initial [3H]oleic acid esterification into total phospholipids was unchanged, within the phospholipid fraction the initial [3H]oleic acid esterification into phosphatidylethanolamine was increased 70% and decreased 50% in phosphatidylcholine in I-FABP expressing cells [10].

Other interactions of Fabp2

• The results indicate that both L-FABP and ilbp levels are modestly increased in the small intestine of chow-fed mice lacking I-FABP [2].
• Finally, the proximal intestine also expresses intestinal-FABP (I-FABP) which decreased 3-fold in the TGF beta 1-deficient/immunodeficient C3H mice only [11].
• The increase in phospholipid levels resulted in dramatic 48 and 33% decreases in the cholesterol-to-phospholipid ratio in L- and I-FABP expressing cells, respectively [9].

Analytical, diagnostic and therapeutic context of Fabp2

• In situ hybridization revealed that the I-FABP mRNA was expressed exclusively in the intestine of the adult zebrafish [6].
• An oligonucleotide probe complementary to the zebrafish I-FABP mRNA hybridized to an mRNA of approximately 800 bases in Northern blot analysis [6].
• Multiple sequence alignment revealed extensive amino acid identity between this zebrafish FABP and intestinal-like FABPs (I-FABP) from other species [6].

References