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：
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
项目类别：
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

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.

项目摘要低密度脂蛋白受体（LDLR）是一种广泛表达的蛋白质，主要以其在肝中的作用而闻名 LDL胆固醇的吸收和清除。像胆固醇一样，类胡萝卜素（例如β-胡萝卜素和叶黄素）由于其疏水性而在LDL颗粒中运输。但是，关于在这些过程中发现的类胡萝卜素的代谢命运以及LDLR的功能。在尤其是LDLR介导透脑胆固醇排泄，已知该胆固醇的排泄最多为 35％的人类胆固醇排泄。是否还可以通过此过程消除类胡萝卜素未知。类胡萝卜素主要存储在肝脏中，但令人惊讶的是，存在一些知识差距类胡萝卜素的肝素代谢，包括LDLR介导类胡萝卜素的肝摄取，或者如果类胡萝卜素（例如胆固醇）修改了VLDL颗粒中分泌的特征。因此，总体该建议的目的是表征LDLR在类胡萝卜素极端和肝摄取中的作用，在研究将类胡萝卜素掺入VLDL颗粒以及如何将VLDL特性掺入改变。我们假设LDLR介导了脑杆菌类胡萝卜素排泄，并有助于肝类胡萝卜素的吸收。我们还假设将肝类胡萝卜素纳入新合成的VLDL 并修改其尺寸和脂质含量。为了检验这些假设，我们提出了三个目标表征LDLR参与类胡萝卜素的吸收和排泄，以及肝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和消除人类。