Isotope Ratio Mass Spectrometer for Nutritional and Metabolic Studies

用于营养和代谢研究的同位素比质谱仪

• 批准号: BB/R00028X/1
• 负责人: Barbara Fielding
• 金额: $ 25.86万
• 依托单位: University of Surrey
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR00028X%2F1
• 关键词: Isotope; Ratio; Mass; Spectrometer; Nutritional

To fully understand how nutrients in our diet are metabolised and promote health or risk of disease, we need to trace molecules such as sugars and fats around the body. The gold-standard method for this is by using stable isotope tracers. These are molecules that have been modified so that one or more of their atoms is replaced with a less common form of the atom (a stable isotope). These tracers are not radioactive; they are safe to give to humans, including children and pregnant women, and they have really shaped our understanding of nutrition and metabolism. For example, if a person ingests a meal containing a specific type of fat that has been labelled with a stable isotope tracer, we can follow the movement of this fat in and out of the blood over the course of time, and independently of other types of fat in the body. We do this by measuring the stable isotope tracer in a series of timed blood samples, using mass spectrometry.It is absolutely vital that we, and others, continue to use this technique to answer fundamental questions about how nutrition and physiology relate to human health, as outlined in the BBSRC's strategic plan. To this end, it is essential for us to update our old equipment (an isotope ratio mass-spectrometer, IRMS) with more reliable, next generation equipment. This will allow us to expand our analytical capability in the use of stable isotope tracer methodology at Surrey, and Nationwide. The more efficient software and hardware will allow us to operate the equipment in such a way as to maximise its use. This will involve widening access to the methodology, by increasing the available time on the machine, and by 'demystifying' the use of the technology through training and promotion. Our aim is train the next generation of undergraduate and postgraduate students, and visiting Fellows, in the use of stable isotope tracers. To help facilitate this aim, we have an industrial sponsor, LGC (The Laboratory of the Government Chemist), who will provide training on quality control procedures, and provide assurance that our measurements are of the highest standard.A major biological challenge of modern life is to understand how the Western diet impacts on human health. We are currently applying stable isotope tracers to address this challenge in three multi-centred studies funded by the BBSRC, one MRC-funded project and two BBSRC doctoral training partnership PhD projects that relate to the UK eating patterns. The first BBSRC study has been designed to better understand why some people's blood cholesterol is very sensitive to changes in the intake of dietary saturated fat, while others people's blood cholesterol shows little or no effect. We will be giving stable isotope labelled saturated fat to 'cholesterol responders' and 'non-responders' to trace the differences in metabolic pathways that might explain this variation in cholesterol response to saturated fat. In another BBSRC DRINC funded project, we will use potatoes that have the starch pre-labelled with an isotope label. This will help us to understand how chilling and reheating a mashed potato meal improves the body's handling of a particular type of starch in the potato. In a third BBSRC study, we will provide new evidence for the health effects of 'inter-esterified' fats that are being introduced by the food industry as substitutes for unhealthy, hydrogenated trans fats. An MRC funded project will examine the impact of the balance of food eaten in the morning and evening on metabolic and behavioural regulation during weight loss. This study will help to understand how energy balance can be modulated by altering meal timing. Finally, our BBSRC DTP students are measuring the intestinal handling of fructose in vivo and in a cell model, and investigating the regulation of enzymes that mediate the conversion of alpha linolenic acid in cooking oils, into long chain polyunsaturated fatty acids. Both of these studies would employ the use of a new IRMS.

为了充分了解我们饮食中的营养物质是如何代谢的，并促进健康或疾病风险，我们需要跟踪身体周围的糖和脂肪等分子。这方面的金标准方法是使用稳定的同位素示踪剂。这些分子已经被修饰，它们的一个或多个原子被不太常见的原子(一种稳定的同位素)取代。这些示踪剂没有放射性；它们对包括儿童和孕妇在内的人类是安全的，它们确实塑造了我们对营养和新陈代谢的理解。例如，如果一个人摄入了一顿含有特定类型脂肪的食物，该脂肪已被标记为稳定的同位素示踪剂，我们可以跟踪这种脂肪在一段时间内流入和流出血液的运动，并且独立于体内其他类型的脂肪。我们通过使用质谱仪测量一系列定时血液样本中的稳定同位素示踪剂来做到这一点。正如BBSRC的战略计划所概述的那样，我们和其他人继续使用这项技术来回答关于营养和生理如何与人类健康相关的基本问题是绝对至关重要的。为此，我们必须用更可靠的下一代设备更新我们的旧设备(同位素比质谱仪，IRMS)。这将使我们能够扩大我们在萨里郡和全国范围内使用稳定同位素示踪方法的分析能力。更高效的软件和硬件将使我们能够以最大限度地利用设备的方式操作设备。这将包括通过增加机器上的可用时间，以及通过培训和推广来“揭开”这项技术的使用的神秘面纱，从而扩大使用该方法的途径。我们的目标是培训下一代本科生和研究生，以及访问研究员，使用稳定的同位素示踪剂。为了达到这个目标，我们有一个工业赞助商LGC(政府化验师实验室)，他将提供有关质量控制程序的培训，并保证我们的测量是最高标准的。现代生活中的一项重大生物学挑战是了解西方饮食对人类健康的影响。我们目前正在BBSRC资助的三项多中心研究中应用稳定同位素示踪剂来应对这一挑战，BBSRC资助的一个项目和BBSRC博士培训伙伴关系的两个博士项目与英国的饮食模式有关。BBSRC的第一项研究旨在更好地了解为什么一些人的血液胆固醇对饮食饱和脂肪摄入量的变化非常敏感，而另一些人的血液胆固醇几乎没有影响。我们将给“胆固醇反应者”和“无反应者”提供标记为饱和脂肪的稳定同位素，以追踪代谢途径的差异，这可能解释了胆固醇对饱和脂肪反应的这种变化。在BBSRC DRINC资助的另一个项目中，我们将使用淀粉预先贴上同位素标签的土豆。这将帮助我们了解冷却和重新加热土豆泥是如何改善人体对土豆中特定类型淀粉的处理能力的。在BBSRC的第三项研究中，我们将提供新的证据，证明“酯间”脂肪对健康的影响，这种脂肪是由食品工业引入的，作为不健康的氢化反式脂肪的替代品。MRC资助的一个项目将研究早晚饮食平衡对减肥期间新陈代谢和行为调节的影响。这项研究将有助于理解如何通过改变进餐时间来调节能量平衡。最后，我们的BBSRC DTP学生正在测量体内和细胞模型中果糖的肠道处理，并研究介导食用油中α-亚麻酸转化为长链多不饱和脂肪酸的酶的调节。这两项研究都将使用一种新的IRMS。

项目成果

Partitioning of a-Linolenic acid metabolism towards 20:3n-3 synthesis rather than 18- carbon oxylipin production alters with age, which is consistent with induction of a more inflammatory phenotype in older individuals

α-亚麻酸代谢向 20:3n-3 合成而不是 18-碳氧脂素产生的分配随着年龄而改变，这与在老年人中诱导更多炎症表型是一致的

• DOI: 10.1017/s0029665122002415
• 发表时间: 2022
• 期刊: Proceedings of the Nutrition Society
• 影响因子: 7
• 作者: Von Gerichten J

The Effect of Fructose Feeding on Intestinal Triacylglycerol Production and De Novo Fatty Acid Synthesis in Humans.

果糖喂养对人体肠道三酰甘油生成和脂肪酸从头合成的影响。

• DOI: 10.3390/nu12061781
• 发表时间: 2020
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Steenson S

Report of a member-led meeting: how stable isotope techniques can enhance human nutrition research

成员主导的会议报告：稳定同位素技术如何加强人类营养研究

• DOI: 10.1017/s0029665120007016
• 发表时间: 2020
• 期刊: Proceedings of the Nutrition Society
• 影响因子: 7
• 作者: Fielding B

The effect of fructose on intestinal triacylglycerol production and de novo fatty acid synthesis in humans and in an enterocyte model

果糖对人类和肠上皮细胞模型中肠道三酰甘油产生和脂肪酸从头合成的影响

• 发表时间: 2019
• 作者: Steenson Simon

How does polyunsaturated fatty acid biosynthesis regulate T-lymphocyte function?

多不饱和脂肪酸生物合成如何调节T淋巴细胞功能？

• DOI: 10.1111/nbu.12404
• 发表时间: 2019
• 期刊: Nutrition Bulletin
• 影响因子: 3.3
• 作者: Fielding B