Function of ileal lipid binding protein

回肠脂质结合蛋白的功能

• 批准号: 371856-2009
• 负责人: Agellon, Luis
• 金额: $ 2.33万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528394
• 关键词: Function; ileal; lipid; binding; protein

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.

脂肪酸结合蛋白（Fatty acid binding proteins，FABPs）是一种存在于多种组织中的小分子量可溶性蛋白质。某些种类的FABP与某些组织类型相关。这些蛋白质共享相似的3D结构，尽管它们的一级结构显著不同。一级结构的差异可能有助于它们对配体的偏好。这些蛋白质的生理功能尚不清楚。这表明，这些蛋白质发挥了重要作用，在细胞的运输和存储各自的配体，这是小的疏水化合物。在小鼠中使用靶向基因技术的研究表明，这些蛋白质的丢失会影响其各自配体的代谢。也有人认为，FABP可能参与基因表达的调控，通过充当内化配体的膜结合转运蛋白和与靶基因启动子结合的同源核受体之间的细胞内穿梭。回肠脂质结合蛋白（ilbp）最初定位于小肠的远端。ILBP可以结合脂肪酸和胆汁酸。胆汁酸是由肝脏从胆固醇合成的两亲分子，并且对于脂质和脂溶性营养素的溶解和吸收是必需的。一些研究者认为，由于ilbp对胆汁酸有更大的亲和力，因此ilbp在胆汁酸的转运和代谢中起主要作用。然而，最近在卵巢中也检测到ilbp，这增加了这种蛋白质可能具有超出胆汁酸代谢的生理功能的可能性。研究计划围绕三个主题展开。在主题I下，我们将使用小鼠作为研究模型系统来探索ILBP在胆汁酸代谢中的生理功能。在主题II下，我们将分析ilbp在非肠细胞（如卵巢细胞）中的作用。在主题III下，我们将探测ilbp配体结合的分子决定簇。这项研究有望为ilbp生物学提供新的见解，并促进我们对FABP作用的全面了解。