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

基本信息

批准号：
10534613
负责人：
Anthony Paul Miller
金额：
$ 4.38万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-30 至 2024-08-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10534613
关键词：
Accounting Animal Model Animals Atherosclerosis Beta Carotene Bile Acids 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 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 Mind 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 base basolateral membrane cell type design feeding insight lipophilicity liver metabolism mutant overexpression particle receptor uptake

项目摘要

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.

项目概要低密度脂蛋白受体 (LDLR) 是一种广泛表达的蛋白质，主要因其在肝脏中的作用而闻名。低密度脂蛋白胆固醇的摄取和清除与胆固醇一样，β-胡萝卜素和叶黄素等类胡萝卜素也是如此。然而，由于其疏水性，LDL 颗粒的运输仍然未知。脂蛋白中类胡萝卜素的代谢命运，以及 LDLR 在这些过程中的功能。特别是，LDLR 已知可介导经肠胆固醇排泄，已知这可解释高达人体中35%的胆固醇是否也通过这个过程被消除？类胡萝卜素主要储存在肝脏中，但令人惊讶的是，肝脏中存在一些知识空白。类胡萝卜素的肝脏代谢，包括 LDLR 是否介导肝脏对类胡萝卜素的摄取，或者如果类胡萝卜素与胆固醇一样，可以改变 VLDL 颗粒的分泌特性。该提案的目的是描述 LDLR 在类胡萝卜素排泄和肝脏摄取中的作用，以及研究类胡萝卜素与 VLDL 颗粒的结合情况以及 VLDL 特性如何变化我们认为 LDLR 介导经肠类胡萝卜素排泄并有助于肝脏。我们还发现肝脏类胡萝卜素被纳入新合成的 VLDL 中。并修改它们的大小和脂质含量为了检验这些假设，我们提出了三个目标。描述 LDLR 参与类胡萝卜素的摄取和排泄，以及肝脏参与这些研究有可能揭示类胡萝卜素运输和运输的关键途径。在人类中消除。