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

动脉粥样硬化是心脏病的主要促成因素，心脏病是美国的主要死亡原因。与肥胖症一起，这两种疾病的发生是因为脂质的过度积累，这也通过引起炎症改变了免疫系统。β-胡萝卜素（β-carotene）是由植物合成的天然色素，也是动物体内维生素A的主要前体。维生素A对于免疫系统功能和脂肪细胞的发育以及因此的肥胖是至关重要的，但是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，尽管血浆和组织中的β-胡萝卜素水平很高，但在野生型小鼠中几乎检测不到β-胡萝卜素，即使在用大量β-胡萝卜素补充其饮食后也是如此。此外，正常小鼠不发生动脉粥样硬化;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。为了克服这些实验局限性，我们与合作者一起产生了一种小鼠模型，该模型模拟β-胡萝卜素的积累并发展动脉粥样硬化，就像人类一样。这种新的模型对于理解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“人源化”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β-胡萝卜素的摄入对小鼠动脉粥样硬化的发展是有益的，以及这种效果与人的关系。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利用特定的小鼠模型来了解β-胡萝卜素对人体维生素A形成的作用。我们希望这种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。

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.