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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：
10563152
负责人：
Jaime Amengual Terrasa
金额：
$ 38.63万
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 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10563152
关键词：
Acceleration Adipocytes Adipose tissue Animal Model Animals Anti-Inflammatory Agents Aorta 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 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 Macrophage 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 caspase 14 design dietary experimental study fatty acid oxidation fighting human disease human tissue immune function immune system function lipid metabolism 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.

动脉粥样硬化是导致心脏病的主要因素，而心脏病是美国人死亡的主要原因。与肥胖一起，这两种疾病的发生都是由于脂肪的过度积累，这也会通过引起炎症来改变免疫系统。β-胡萝卜素（β-胡萝卜素）是一种由植物合成的天然色素，是动物体内维生素a的主要前体。维生素A对免疫系统功能和脂肪细胞的发育至关重要，因此对肥胖至关重要，但β-胡萝卜素和维生素A与动脉粥样硬化和肥胖的相关性很少。在人类中，尽管血浆和组织中β-胡萝卜素的含量很高，但即使在野生型小鼠的饮食中补充了大量β-胡萝卜素，也几乎检测不到β-胡萝卜素。此外，正常小鼠不会发生动脉粥样硬化；因此，研究β-胡萝卜素在动脉粥样硬化和肥胖中的作用需要特殊的动物模型。为了克服这些实验的局限性，我们和我们的合作者一起建立了一个小鼠模型，模拟β-胡萝卜素的积累并发展成动脉粥样硬化，就像人类一样。这个新模型对于理解β-胡萝卜素对维生素A产生的作用至关重要，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有益，以及这种效果与人类的关系。其次，我们将使用我们的小鼠模型来研究血浆β-胡萝卜素在动脉粥样硬化和肥胖发展过程中对免疫细胞的作用。最后，我们将开发一种技术，利用储存在脂肪组织中的β-胡萝卜素来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影响。本研究的总体目标是通过使用特定的小鼠模型来了解β-胡萝卜素在人类维生素A形成中的作用。我们希望这一方法将有助于我们的社会考虑摄入和储存β-胡萝卜素作为治疗动脉粥样硬化和肥胖的潜在治疗策略。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Fenretinide inhibits vitamin A formation from β-carotene and regulates carotenoid levels in mice.

DOI：
10.1016/j.bbalip.2021.159070
发表时间：
2022-03
期刊：
Biochimica et biophysica acta. Molecular and cell biology of lipids
影响因子：
0
作者：
Miller AP;Black M;Amengual J
通讯作者：
Amengual J

The conversion of β-carotene to vitamin A in adipocytes drives the anti-obesogenic effects of β-carotene in mice.

DOI：
10.1016/j.molmet.2022.101640
发表时间：
2022-12
期刊：
MOLECULAR METABOLISM
影响因子：
8.1
作者：
Coronel, Johana;Yu, Jianshi;Pilli, Nageswara;Kane, Maureen A.;Amengual, Jaume
通讯作者：
Amengual, Jaume

Lycopene: A Critical Review of Digestion, Absorption, Metabolism, and Excretion.

DOI：
10.3390/antiox10030342
发表时间：
2021-02-25
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
0
作者：
Arballo J;Amengual J;Erdman JW Jr
通讯作者：
Erdman JW Jr

Bioavailability and provitamin A activity of neurosporaxanthin in mice.

DOI：
10.1038/s42003-023-05446-1
发表时间：
2023-10-20
期刊：
COMMUNICATIONS BIOLOGY
影响因子：
5.9
作者：
Miller, Anthony P.;Hornero-Mendez, Damaso;Bandara, Sepalika;Parra-Rivero, Obdulia;Limon, M. Carmen;von Lintig, Johannes;Avalos, Javier;Amengual, Jaume
通讯作者：
Amengual, Jaume

Monocytes and macrophages in atherogenesis.