Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, OH, United States of America.
Department of Comparative Medicine, University of Washington, Seattle, WA, United States of America.
Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Aug;1867(8):159179. doi: 10.1016/j.bbalip.2022.159179. Epub 2022 May 6.
Retinol-binding protein 2 (RBP2, also known as cellular retinol-binding protein 2 (CRBP2)) is a member of the fatty acid-binding protein family and has been extensively studied for its role in facilitating dietary vitamin A (retinol) uptake and metabolism within enterocytes of the small intestine. RBP2 is present in highest concentrations in the proximal small intestine where it constitutes approximately 0.1-0.5% of soluble protein. Recent reports have established that RBP2 binds monoacylglycerols (MAGs) with high affinity, including the canonical endocannabinoid 2-arachidonoylglycerol (2-AG). Crystallographic studies reveal that retinol, 2-AG, or other long-chain MAGs alternatively can bind in the retinol-binding pocket of RBP2. It also has been demonstrated recently that Rbp2-deficient mice are more susceptible to developing obesity and associated metabolic phenotypes when exposed to a high fat diet, or as they age when fed a conventional chow diet. When subjected to an oral fat challenge, the Rbp2-deficient mice release into the circulation significantly more, compared to littermate controls, of the intestinal hormone glucose-dependent insulinotropic polypeptide (GIP). These new findings regarding RBP2 structure and actions within the intestine are the focus of this review.
视黄醇结合蛋白 2（RBP2，也称为细胞视黄醇结合蛋白 2（CRBP2））是脂肪酸结合蛋白家族的成员，因其在促进小肠肠细胞中膳食维生素 A（视黄醇）摄取和代谢中的作用而得到广泛研究。RBP2 在小肠近端浓度最高，约占可溶性蛋白的 0.1-0.5%。最近的报告表明，RBP2 与单酰基甘油（MAGs）具有高亲和力结合，包括典型的内源性大麻素 2-花生四烯酸甘油（2-AG）。晶体学研究表明，视黄醇、2-AG 或其他长链 MAG 可以替代地结合到 RBP2 的视黄醇结合口袋中。最近还证明，当暴露于高脂肪饮食或在喂食常规饲料时随着年龄的增长，缺乏 Rbp2 的小鼠更容易发展为肥胖和相关代谢表型。当接受口服脂肪挑战时，与同窝对照相比，缺乏 Rbp2 的小鼠释放到循环中的肠激素葡萄糖依赖性胰岛素释放肽（GIP）明显更多。本综述的重点是关于 RBP2 在肠道中的结构和作用的这些新发现。
