The Vitamin A Laboratory (VitAL) research program: fundamental insight into vitamin A metabolism

维生素A是维持人类和其他动物健康所必需的微量营养素。自100多年前被发现以来，人们对维生素A的生物学已经有了很多了解；然而，关于它的新陈代谢和功能，我们的知识仍然存在根本的空白。维生素A是完成人体一些最基本的功能所必需的，在视力、免疫力和生殖方面起着关键作用。发展中国家强调了摄取足够的维生素A的必要性，在那里，维生素A缺乏与婴儿死亡率高和儿童失明有关。虽然维生素A缺乏在加拿大并不是一个主要问题，但维生素A功能受损对某些癌症、出生缺陷和代谢性疾病的影响，突显了它的重要性。考虑到这一点，维生素A实验室(VITAL)研究计划的总体目标是提高我们对基本维生素A生物学的了解。我们的研究计划侧重于更好地了解人体如何处理和使用维生素A。我们对肝脏特别感兴趣，因为肝脏是人体的维生素A仓库和分配中心。具体地说，肝脏含有体内最大的维生素A，并以稳定的速度分泌，以供应身体的其余部分。根据我们的初步数据，我们已经确定了脂肪酸转运蛋白CD36在维生素A代谢中的一个以前未被认识到的作用。这项拟议的工作涉及在整个有机体、细胞和分子水平上研究CD36，并检验CD36是肝脏维生素A代谢的新贡献者这一中心假设。在方法上，这项工作将包括研究CD36基因敲除小鼠，抑制CD36在分离的肝细胞中的功能，以及在分子水平上分析维生素A与CD36的相互作用。提高我们对维生素A代谢的基本理解是至关重要的。这项提案中描述的新颖工作将导致CD36被确认为迄今未被认识到的维生素A生物学贡献者，这是该领域的一项重要发现。这一新知识将与那些对生命科学感兴趣的人相关，包括营养学家、生理学家和生化学家。就加拿大而言，该国在向发展中国家提供维生素A补充剂方面享誉全球。被称为“加拿大的维生素A成功故事”的维生素A补充剂，通过微营养素倡议提供，并由加拿大政府资助，帮助拯救了数百万儿童的生命。通过建立一个国际公认的研究维生素A生物学的卓越计划，我们的工作将进一步提高加拿大的声誉和影响力，提供一个基本的科学计划，以补充该国在全球卫生努力中已确立的卓越成就。

Vitamin A is an essential micronutrient, required to maintain good health in humans and other animals. Since its discovery over 100 years ago, much has been learned about vitamin A biology; however, there remain fundamental gaps in our knowledge concerning its metabolism and function. Vitamin A is required to fulfill some of the body's most basic functions, with critical roles in vision, immunity and reproduction. The necessity of adequate vitamin A intake is highlighted in the developing world, where its deficiency is associated with high infant mortality and childhood blindness. Although vitamin A deficiency is not a major issue in Canada, the contribution of impaired vitamin A function to certain cancers, birth defects and metabolic diseases, underscores its importance. With this in mind, the overall goal of the Vitamin A Laboratory's (VitAL) research program is to improve our understanding of basic vitamin A biology.Our research program focuses on providing a better understanding of how the body processes and uses vitamin A. We are particularly interested in the liver, because this organ serves as the body's vitamin A warehouse and distribution center. Specifically, the liver contains the largest store of vitamin A in the body, and secretes it at a steady rate to supply the rest of the body. Based on our preliminary data, we have identified a previously unrecognized role for the fatty acid transporter CD36 in vitamin A metabolism. The proposed work involves studying CD36 at the whole organism, cellular, and molecular level, and tests the central hypothesis that CD36 is a novel contributor to hepatic vitamin A metabolism. Methodologically, this work will involve studying Cd36 knockout mice, inhibiting CD36 function in isolated liver cells, and assaying vitamin A-CD36 interactions at the molecular level.Improving our basic understanding of vitamin A metabolism is fundamentally important. The novel work described in this proposal will lead to the identification of CD36 as a hitherto unrecognized contributor to vitamin A biology, representing an important discovery in the field. This new knowledge will be relevant to those interested in the life sciences, including nutritionists, physiologists and biochemists. In the Canadian context, this country has a global reputation in providing vitamin A supplements to the developing world. Dubbed “Canada's vitamin A success story”, vitamin A supplements provided through the Micronutrient Initiative, and funded by the Canadian government, have helped save millions of children's lives. By establishing an internationally recognized program of excellence into studying vitamin A biology, our work will further bolster Canada's reputation and impact, providing a basic scientific program to complement the established excellence in the country's global health efforts.