Liquid Chromatography-Mass Spectrometry for the Analysis of Biological Small Molecules in Metabolomic, Nutritional, and Toxicological Studies.

该提案要求支持一种名为液质联用仪(LC-MS)的设备。这种设备使研究人员能够测量颗粒的质量，并找到组成生物样本的基本化学物质，如血液、组织或食物。该提案中要求的LC-MS将支持来自多个科学学科的研究，以及几个对人群健康非常重要的不同项目：示例项目1：鉴于全球有3.4亿人患有2型糖尿病，找到新的治疗方法至关重要。白色脂肪组织以脂肪的形式储存能量，并向血液中释放信号，与其他器官沟通，调节全身新陈代谢。然而，并不是所有的脂肪细胞都是一样的。第二种脂肪细胞是棕色脂肪细胞，它通过“燃烧”储存的脂肪来调节体温，产生热量。第三种脂肪细胞群，米色脂肪，可以从表现为白色脂肪细胞(储存脂肪)转变为功能类似棕色脂肪细胞(燃烧脂肪)，这一过程被称为“褐变”。在人类中，米色脂肪可能构成了这种产热组织的大部分，白色脂肪组织中也有米色脂肪。米色脂肪具有抗糖尿病的特性，这在一定程度上可能是通过向血液中释放信号来实现的，这些信号改变了肝脏、肌肉和白色脂肪等组织的新陈代谢。这项研究将使用所要求的LC-MS来确定白色脂肪组织的褐变是否导致代谢物信号分泌，并识别这些信号。将调查代谢产物信号在邻近白色脂肪组织中诱导褐变的能力，以及通过血液向其他器官发出信号以调节全身新陈代谢的能力。这项研究可能会识别具有抗肥胖特性的米色细胞特定代谢物信号，并提供新的抗糖尿病疗法。例如，项目2：食物成分可以对健康的广泛方面产生深远影响，包括肠道功能、血糖控制和我们的思维能力。小麦和其他粮食作物含有天然存在的化合物，称为酚类，这种化合物可能具有抗氧化作用，可以减少细胞对DNA的损害，而DNA是癌症和衰老的重要因素。它们还可以改善肠道功能。这个项目将使用LC-MS来测量肠道功能模型中的抗氧化酚和微量营养素，以了解这些抗氧化剂酚从食物中被吸收的难易程度，确定改善其吸收的方法，并测量存在酚的情况下其他微量营养素在肠道中的吸收，以确定它们如何影响肠道营养物质的吸收。范例项目3：食品污染物和毒素是对人类健康的重大威胁，对低收入国家的弱势社区有特别的影响。一组特殊的毒素被称为真菌毒素，来自真菌，可以污染玉米和小麦等粮食作物，并与儿童生长发育减慢和癌症的发展有关。该项目将使用所要求的LC-MS来测量毒素水平和非洲人口中接触毒素的标志，以了解不同作物、储存条件和地理位置中污染物的分布模式，并评估降低非洲真菌毒素风险的干预措施的有效性。例如，项目4：暴露在空气交通颗粒物形式的环境污染中，会改变血液凝块的方式，并导致深静脉血栓形成。该项目将使用所要求的LC-MS来测量人群血液样本中暴露于颗粒污染物的标志物，以了解污染对心血管健康的影响。

This proposal requests support for a piece of equipment called a liquid chromatography - mass spectrometer (LC-MS). This equipment allows researchers to measure the mass of particles, and to find the basic chemicals that make up a biological sample such as blood, tissue or food. The LC-MS requested in this proposal will support research from multiple scientific disciplines, and on several distinct projects of great importance to the health of the population:Example Project 1: Given that 340 million people worldwide suffer from type 2 diabetes, finding new treatments is essential. White fat tissue stores energy as fat and releases signals into the blood which communicate with other organs, regulating whole-body metabolism. However, not all fat cells are identical. A second fat cell population, brown fat cells, regulate body temperature by "burning" stored fats, producing heat. A third fat cell population, beige fat, can switch from behaving like white fat cells (storing fat) to functioning like brown fat cells (burning fat), a process called "browning". In humans, beige fat may form the majority of this heat-producing tissue, and is also found within white fat tissue. Beige fat has anti-diabetic properties which may, in part, occur through release of signals into the blood which alter metabolism in tissues such as liver, muscle and white fat.This research will use the requested LC-MS to determine whether browning of white fat tissue results in metabolite signal secretion, and to identify these signals. The capacity of metabolite signals to induce browning in neighbouring white fat tissue and to signal, via the blood, to other organs to regulate whole-body metabolism, will be investigated. This research may identify beige cell-specific metabolite signals, with anti-obesity properties, and provide new anti-diabetic therapies.Example Project 2: Food constituents can have profound effects on wide ranging aspects of health including gut function, control of blood glucose and our ability to think. Wheat and other food crops contain naturally occurring compounds, called phenols, which may have anti-oxidant effects that reduce cellular damage to DNA known to be important in cancer and ageing. They may also improve gut function. This project will use the LC-MS to measure the antioxidant phenols, and micronutrients in models of gut function to understand how readily these antioxidant phenols are absorbed from food, determine ways of improving their uptake, and to measure the absorption of other micronutrients across the gut in the presence of the phenols to determine how they affect gut nutrient uptake. Example Project 3: Food contaminants and toxins are a major risk to human health and have particular impact on vulnerable communities in low income countries. A particular group of toxins know as mycotoxins, derived from fungus, can contaminate food crops such as maize and wheat and have been linked to reduced child growth and development, and the development of cancer. This project will use the requested LC-MS to measure levels of the toxins and markers of exposure to the toxins in human populations from Africa to understand distribution patterns of contamination in different crops, storage conditions and geographic locations and to assess the effectiveness of interventions to reduce mycotoxin risk in Africa. Therefore contributing to the safety and security of the global food industry.Example Project 4: Exposure to environmental pollution in the form of particulates from traffic in the air can alter the way in which blood clots and contribute to deep vein thrombosis. This project will use the requested LC-MS to measure markers of exposure to the particle pollutants in blood samples of the population to understand the effects of pollution on cardiovascular health.