Function of ileal lipid binding protein

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Fatty acid binding proteins (FABPs) are abundant, small molecular weight soluble proteins found in a wide variety of tissues. Certain species of FABPs are associated with certain tissue types. These proteins share similar 3D structures despite significant dissimilarity in their primary structures. The divergence in primary structure likely contributes to their preference of ligands. The physiological function of these proteins is not precisely known. It is suggested that these proteins play an important role in the cellular transport and storage of their respective ligands, which are small hydrophobic compounds. Studies using targeted gene technology in mice suggest that the loss of these proteins affects the metabolism of their respective ligands. It has also been suggested that FABPs may be involved in regulation of gene expression, by serving as the intracellular shuttle between the membrane-bound transporter that internalizes the ligand and the cognate nuclear receptor that is bound to the promoters of target genes. The ileal lipid binding protein (ilbp) was initially localized in the distal portion of the small intestine. Ilbp can bind both fatty acids and bile acids. Bile acids are amphipathic molecules synthesized by the liver from cholesterol, and are essential for the solubilization and absorption of lipids and lipid-soluble nutrients. Some investigators have suggested that ilbp plays a major role in bile acid transport and metabolism, due to the greater affinity of ilbp for bile acids. Recently however, ilbp has also been detected in the ovaries, raising the possibility that this protein may have a physiological function beyond bile acid metabolism. The proposed research program is constructed around three themes. Under Theme I, we will explore the physiological function of ILBP in the metabolism of bile acids using mice as a model system of study. Under Theme II, we will analyze the role of ilbp in non-intestinal cells, such as ovary cells. Under Theme III, we will probe the molecular determinants of ilbp ligand binding. The proposed research is anticipated to give new insights on ilbp biology as well as advance our general understanding of FABP action.