To study the role of the low-density lipoprotein receptor on carotenoid biodistribution and excretion

研究低密度脂蛋白受体对类胡萝卜素生物分布和排泄的作用

• 批准号: 10329186
• 负责人: Jaime Amengual Terrasa
• 金额: $ 14.93万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10329186
• 关键词: Animal Model; Atherosclerosis; Beta Carotene; Biodistribution; Carotenoids; Cleaved cell; Color; Dietary Carotenoid; Enzymes; Excretory function; Feces; Food; Health Promotion; Human; Intestines; Knockout Mice; Knowledge; Low Density Lipoprotein Receptor; Lutein; Mammals; Methodology; Mouse Strains; Mus; Oxygenases; Parents; Physiology; Plasma; Process; Provitamin A Carotenoid; Role; Tissues; Vitamin A; disorder prevention; fruits and vegetables; mouse model; mutant; novel

PROJECT SUMMARY Carotenoids are a diverse group of compounds responsible for the yellow-to-red colors in fruits and vegetables. These compounds are widely considered to be among the most important bioactive compounds in our food. Carotenoids can be divided in provitamin A carotenoids such as β-carotene, and non-provitamin A carotenoids such as lutein. While the role of carotenoids in the promotion of health and the prevention of disease in humans is clear, little is known about the mechanisms that control the distribution and excretion of these compounds. This gap in knowledge occurs, at least in part, due to the lack of reliable animal models to study carotenoid accumulation that mimic human carotenoid physiology. For instance, the enzymes responsible of carotenoid degradation, which are present in all mammals, are extremely active in mice but not in humans, which leads to the accumulation of dietary carotenoids in our tissues, in contrast to what occurs in mice. The only way to overcome this technical limitation is to rely on knockout mouse models for β-carotene oxygenase 1 (BCO1), which cleaves β-carotene, and BCO2, which cleaves lutein and other carotenoids. In our parent R01, we aim to determine the role of β-carotene and vitamin A on atherosclerosis, and to this end, we combined mice lacking BCO1 and the low-density lipoprotein receptor (LDLR). As a result, these compound mice accumulate carotenoids and develop atherosclerosis due to the lack of BCO1 and LDLR, respectively. We are in the process of generating compound mutants lacking BCO2 and LDLR, in which we will be able to study the role of LDLR in lutein accumulation. By using these two novel new mouse strains to single BCO1 and BCO2, we will study the role of LDLR in (1) carotenoid biodistribution, and (2) intestinal elimination. Using state of the art methodologies to quantify these compounds in tissues, plasma, and feces, we will establish the role of the LDLR in carotenoid transport.

项目摘要 类胡萝卜素是一组潜水员，这些化合物负责水果中的黄色至红色颜色 蔬菜。这些化合物被普遍认为是最重要的生物活性之一 食物中的化合物。类胡萝卜素可以在类胡萝卜素（例如β-胡萝卜素）和 非抗毒素A类胡萝卜素（如叶黄素）。 类胡萝卜素在促进健康和预防人类疾病中的作用是 清楚，对控制这些分布和排泄的机制知之甚少 化合物。知识上的这种差距至少部分是由于缺乏可靠的动物模型 研究类胡萝卜素积累，模仿人类类胡萝卜素生理。例如，酶 在所有哺乳动物中都存在的类胡萝卜素降解，在小鼠中非常活跃 但在人类中，这不是在我们的时间内导致饮食类胡萝卜素积累的，与 在小鼠中发生的事情。克服这一技术限制的唯一方法是依靠淘汰赛鼠标 裂解β-胡萝卜素和BCO2的β-胡萝卜素氧合酶1（BCO1）的模型，它裂解叶黄素 和其他类胡萝卜素。 在我们的母体R01中，我们旨在确定β-胡萝卜素和维生素A对动脉粥样硬化的作用，以及 这端，我们组合了缺乏BCO1的小鼠和低密度脂蛋白受体（LDLR）。因此， 这些复合小鼠会积累类胡萝卜素，并由于缺乏BCO1和 LDLR分别。我们正在生成缺乏BCO2和LDLR的复合突变体， 我们将能够研究LDLR在叶黄素积累中的作用。 通过将这两种新的新小鼠菌株用于单个BCO1和BCO2，我们将研究LDLR在 （1）类胡萝卜素生物分布和（2）肠道消除。使用最先进的方法 量化这些化合物在组织，血浆和粪便中，我们将确定LDLR在 类胡萝卜素运输。