Effects of beta-carotene on vitamin A production in atherosclerosis and obesity

β-胡萝卜素对动脉粥样硬化和肥胖症中维生素 A 产生的影响

基本信息

批准号：
10364751
负责人：
Jaime Amengual Terrasa
金额：
$ 38.66万
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：
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/10364751
关键词：
Adipocytes Adipose tissue Animal Model Animals Anti-Inflammatory Agents Applications Grants Arterial Fatty Streak Atherosclerosis Beta Carotene Biological Assay Blood Bone Marrow Transplantation Bypass Cause of Death Cells Characteristics Chemicals Chronic Clinical Coculture Techniques Color Data Dependovirus Development Diet Disease Doctor of Philosophy Economic Burden Etiology Gene Expression Genetic Transcription Goals Health Heart Diseases Hepatic Human Immune Immune system Inflammation Inflammatory Ingestion Intestines Intracellular Accumulation of Lipids Knockout Mice Lesion Lipids Lipoproteins Liver Low Density Lipoprotein Receptor Mediating Metabolic Metabolism Modeling Mus Obesity Oranges Oxygenases Pathogenesis Persons Phenotype Physiological Pigments Plants Plasma Play Process Production Property Regulatory T-Lymphocyte Research Rodent Role Societies Supplementation T cell differentiation T-Lymphocyte Techniques Testing Therapeutic Thermogenesis Time Tissues Tretinoin Vitamin A Wild Type Mouse adipocyte differentiation analog atherosclerosis risk base caspase 14 design dietary experimental study fatty acid oxidation fighting health economics human disease human tissue immune function immune system function lipid metabolism macrophage monocyte mouse model novel obesity development overexpression post-doctoral training recruit side effect therapeutic target trafficking

项目摘要

Atherosclerosis is the principal contributing factor of heart disease, the main cause of death in the US. Together with obesity, the development of these two diseases occurs because of an excessive accumulation of lipids, which also alters the immune system by causing inflammation. Beta-carotene (β-carotene) is a natural pigment synthesized by plants and the main precursor of vitamin A in animals. Vitamin A is crucial for the immune system function and for the development of adipocytes and therefore obesity, but the relevance of β-carotene and vitamin A on atherosclerosis and obesity is scarce. In humans, even though the levels of β-carotene in plasma and tissues are high, β-carotene is hardly detectable in wild-type mouse even after supplementing their diet with large amounts of β-carotene. Additionally, normal mice do not develop atherosclerosis; therefore, to study the effect of β-carotene in atherosclerosis and obesity demands special animal models. To overcome these experimental limitations, we have generated, together with our collaborators, a mouse model that mimics the accumulation of β- carotene and develops atherosclerosis, as occurs with humans. This novel model is essential to understand the role that β-carotene plays on vitamin A production, and will help us to study these two common human diseases in a “humanized” animal model. First, we will investigate why the ingestion of β-carotene is beneficial against the development of atherosclerosis in mice, and how this effect relates to people. Second, we will use our mouse model to study the function that plasma β-carotene has on immune cells during atherosclerosis and obesity development. Lastly, we will develop a technique to take advantage of the β- carotene stored in adipose tissue to stimulate the production of vitamin A in adipocytes, which will have beneficial effects on obesity and atherosclerosis. The overall goal of this study is to understand the role of β-carotene on vitamin A formation in humans by utilizing a specific mouse model. We hope that this approach will help our society to consider ingested and stored β-carotene as a potential therapeutic strategy to treat atherosclerosis and obesity.

动脉粥样硬化是心脏病的主要因素，这是美国死亡的主要原因。与肥胖症一起，这两种疾病的发展是由于脂质的过量积累而发生的，这也通过引起感染来改变免疫系统。 β-胡萝卜素（β-胡萝卜素）是一种由植物合成的天然色素，也是动物中维生素A的主要前体。维生素A对免疫系统功能和脂肪细胞的发展至关重要，因此对于肥胖症至关重要，但是β-胡萝卜素和维生素A对动脉粥样硬化和肥胖的相关性很少。在人类中，即使血浆和组织中的β-胡萝卜素水平较高，即使在补充了大量β-胡萝卜素的饮食后，野生型小鼠也几乎无法检测到β-胡萝卜素。另外，正常小鼠不会发展动脉粥样硬化。因此，研究β-胡萝卜素在动脉粥样硬化和肥胖症中的作用需要特殊的动物模型。为了克服这些实验局限性，我们与合作者一起生成了一种模仿β-胡萝卜素积累并发展动脉粥样硬化的小鼠模型，就像人类一样。这种新颖的模型对于了解β-胡萝卜素在维生素A生产中起的作用至关重要，并将帮助我们在“人性化”动物模型中研究这两种常见的人类疾病。首先，我们将研究为什么摄入β-胡萝卜素对小鼠动脉粥样硬化的发展以及这种影响与人的关系有益。其次，我们将使用小鼠模型研究血浆β-胡萝卜素在动脉粥样硬化和肥胖发育过程中对免疫细胞的功能。最后，我们将开发一种技术来利用脂肪组织中储存的β-胡萝卜素，以刺激脂肪细胞中维生素A的产生，这将对肥胖和动脉粥样硬化产生有益的作用。这项研究的总体目标是通过利用特定的小鼠模型来了解β-胡萝卜素在人类中的维生素A形成的作用。我们希望这种方法将帮助我们的社会考虑摄入和储存的β-胡萝卜素作为治疗动脉粥样硬化和肥胖症的潜在治疗策略。