Examining the role of LDLR in the biodistribution of carotenoids

检查 LDLR 在类胡萝卜素生物分布中的作用

• 批准号: 10709514
• 负责人: Anthony Paul Miller
• 金额: $ 2.44万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-30 至 2023-12-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10709514
• 关键词: Accounting; Animal Model; Animals; Atherosclerosis; Beta Carotene; Bile Acids; Binding; Biodistribution; Biological Assay; Blood; Carotenoids; Characteristics; Cholesterol; Coupled; Critical Pathways; Data; Dependovirus; Diet; Dietary Intervention; Disease; Electron Microscopy; Endocytosis; Enterocytes; Enzymes; Excretory function; Extrahepatic; Eye; Future; Harvest; Hepatic; Hepatic Tissue; Hepatocyte; High Pressure Liquid Chromatography; Human; Hydrophobicity; Incidence; Intervention; Intestines; Knowledge; LDL Cholesterol Lipoproteins; Light; Lipids; Lipoproteins; Liver; Low Density Lipoprotein Receptor; Low-Density Lipoproteins; Lutein; Malignant Neoplasms; Measures; Mediating; Metabolic; Metabolism; Modeling; Modification; Mus; Nature; Nutrient; Obesity; Organism; Oxygenases; Photosynthesis; Pigments; Plasma; Play; Process; Property; Proteins; Provitamin A Carotenoid; Radiolabeled; Research; Rodent; Role; Testing; Tissues; Ultraviolet Rays; Very low density lipoprotein; Visualization; Vitamin A; basolateral membrane; cell type; design; feeding; insight; lipophilicity; liver metabolism; mutant; overexpression; particle; receptor; uptake

PROJECT SUMMARY The low-density lipoprotein receptor (LDLR) is a widely expressed protein known mostly for its role in hepatic uptake and clearance of LDL cholesterol. Like cholesterol, carotenoids such as β-carotene and lutein are transported in LDL particles due to their hydrophobic nature. There remains, however, unknowns about the metabolic fate of carotenoids found in lipoproteins, as well as the function of LDLR in these processes. In particular, LDLR is known to mediate transintestinal cholesterol excretion, which is known to account for up to 35% of cholesterol excretion in humans. Whether carotenoids are also eliminated through this process is unknown. Carotenoids are primarily stored in the liver, but surprisingly, several knowledge gaps exist in the hepatic metabolism of carotenoids, including if LDLR mediates the hepatic uptake of carotenoids, or if carotenoids, like cholesterol, modify the characteristics of secreted in VLDL particles. Therefore, the overarching objective of this proposal is to characterize the role of LDLR in carotenoid excretion and hepatic uptake, as well as examine the incorporation of carotenoids into VLDL particles and how VLDL characteristics are consequently altered. We hypothesize that LDLR mediates transintestinal carotenoid excretion and contributes to hepatic carotenoid uptake. We also hypothesize that hepatic carotenoids are incorporated into newly-synthesized VLDL and modify their size and lipid content. To test these hypotheses, we propose three objectives that will characterize the involvement of LDLR in carotenoid uptake and excretion, as well as hepatic participation in carotenoid distribution. These studies have the potential to reveal critical pathways in carotenoid transport and elimination in humans.

项目摘要 低密度脂蛋白受体（LDLR）是一种广泛表达的蛋白质，已知其主要在肝脏中的作用。 LDL胆固醇的摄取和清除。像胆固醇一样，类胡萝卜素如β-胡萝卜素和叶黄素也是 由于其疏水性，在低密度脂蛋白颗粒中运输。然而，关于这一点仍然存在未知数。 脂蛋白中发现的类胡萝卜素的代谢命运，以及LDLR在这些过程中的功能。在 特别地，已知LDLR介导经肠胆固醇排泄，已知其导致高达 人体内35%的胆固醇排泄。类胡萝卜素是否也通过这个过程被消除， 未知类胡萝卜素主要储存在肝脏中，但令人惊讶的是， 类胡萝卜素的肝脏代谢，包括LDLR是否介导类胡萝卜素的肝脏摄取，或者 类胡萝卜素与胆固醇一样，改变VLDL颗粒中分泌的特征。因此， 本提案的目的是描述LDLR在类胡萝卜素排泄和肝脏摄取中的作用，以及 作为检查类胡萝卜素纳入VLDL颗粒和VLDL特性如何因此 改变了我们推测LDLR介导了类胡萝卜素的经肠排泄，并促进了肝脏的 类胡萝卜素摄取我们还推测，肝类胡萝卜素纳入新合成的极低密度脂蛋白 并改变它们的大小和脂质含量为了验证这些假设，我们提出了三个目标， 表征LDLR参与类胡萝卜素摄取和排泄，以及肝脏参与 类胡萝卜素分布这些研究有可能揭示类胡萝卜素转运的关键途径， 消除在人类。