The role of chain length in fatty acid uptake in both health and disease: a combined experimental-theoretical modelling approach

链长在健康和疾病中脂肪酸摄取中的作用：实验与理论相结合的建模方法

• 批准号: MR/T003391/2
• 负责人: Patricia Thomas
• 金额: $ 39.27万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT003391%2F2
• 关键词: role; chain; length; fatty; acid

Heart disease, type 2 diabetes and obesity (collectively known as metabolic syndrome) are three of the most serious health conditions facing the UK today. They affect one in four adults in the UK, costing the NHS over £10 billion annually. These figures are rising rapidly, with 1 in 2 people predicted to be affected by 2050, with an associated cost of £50 billion. Sadly, we do not know the basic mechanisms of how type 2 diabetes (and many other obesity-related conditions) occur. Establishing the mechanics and role of fats is critical since too many entering our cells can contribute to the development of diabetes. This then poses the question: how do fats enter cells? At present, we know very little. Identifying how fats enter cells will pave the way for the development of new diets and drug treatments to reduce fat uptake. In the long term, this will help to slow and potentially halt the development of type 2 diabetes, obesity and heart disease.I will use imaging techniques to measure how much fat crosses into cells, how quickly this happens, and how this changes with different types of fats. I will then use this information to build mathematical models that explain the mechanisms behind fat uptake. Although it may seem surprising that mathematics can be used to answer questions in biology, recent progress has shown that combining these two areas can lead to great advances in physiology and medicine. In this project, I will take advantage of my mathematical model to make predictions about the ways in which fats enter cells. I can then confirm or reject these predictions through experiments in the lab. With a good understanding of fat uptake, I will be able to start testing drug treatments and diets in rodents to prevent the progression of type 2 diabetes and obesity.

心脏病、2型糖尿病和肥胖症（统称为代谢综合征）是当今英国面临的三大最严重的健康问题。他们影响了英国四分之一的成年人，每年花费NHS超过100亿英镑。这些数字正在迅速上升，预计到2050年，每2人中就有1人将受到影响，相关成本将达到500亿英镑。可悲的是，我们不知道2型糖尿病（以及许多其他肥胖相关疾病）发生的基本机制。建立脂肪的机制和作用至关重要，因为过多的脂肪进入我们的细胞会导致糖尿病的发展。这就提出了一个问题：脂肪是如何进入细胞的？目前，我们所知甚少。确定脂肪如何进入细胞将为开发新的饮食和药物治疗方法铺平道路，以减少脂肪摄入。从长远来看，这将有助于减缓并可能阻止2型糖尿病、肥胖和心脏病的发展。我将使用成像技术来测量有多少脂肪进入细胞，这一过程发生的速度有多快，以及不同类型的脂肪如何变化。然后，我将使用这些信息来建立数学模型，解释脂肪摄取背后的机制。虽然数学可以用来回答生物学问题似乎令人惊讶，但最近的进展表明，将这两个领域结合起来可以导致生理学和医学的巨大进步。在这个项目中，我将利用我的数学模型来预测脂肪进入细胞的方式。然后，我可以通过实验室的实验来证实或否定这些预测。有了对脂肪摄取的良好理解，我将能够开始测试啮齿动物的药物治疗和饮食，以防止2型糖尿病和肥胖的进展。

项目成果

Differential routing and disposition of the long-chain saturated fatty acid palmitate in rodent vs human beta-cells.

• DOI: 10.1038/s41387-022-00199-y
• 发表时间: 2022-04-20
• 期刊: NUTRITION & DIABETES
• 影响因子: 6.1
• 作者: Thomas, Patricia;Arden, Catherine;Corcoran, Jenna;Hacker, Christian;Welters, Hannah J.;Morgan, Noel G.
• 通讯作者: Morgan, Noel G.