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

液相色谱-质谱法用于代谢组学、营养学和毒理学研究中生物小分子的分析。

• 批准号: BB/R013500/1
• 负责人: Lee Roberts
• 金额: $ 22.01万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR013500%2F1
• 关键词: Liquid; Chromatography; Mass; Spectrometry; Analysis

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.

该提案要求支持一种称为液相色谱-质谱仪的设备。该设备使研究人员能够测量颗粒的质量，并找到构成生物样品（如血液，组织或食物）的基本化学物质。本提案中要求的LC-MS将支持多个科学学科的研究，以及对人口健康非常重要的几个不同项目：示例项目1：鉴于全球有3.4亿人患有2型糖尿病，寻找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，并非所有的脂肪细胞都是相同的。第二种脂肪细胞群，棕色脂肪细胞，通过“燃烧”储存的脂肪产生热量来调节体温。第三种脂肪细胞群，米色脂肪，可以从行为像白色脂肪细胞（储存脂肪）转变为功能像棕色脂肪细胞（燃烧脂肪），这一过程称为“布朗宁”。在人类中，米色脂肪可能构成这种产热组织的大部分，并且也存在于白色脂肪组织中。米色脂肪具有抗糖尿病特性，其可能部分通过向血液中释放信号而发生，所述信号改变组织（如肝脏、肌肉和白色脂肪）中的代谢。本研究将使用所要求的LC-MS来确定白色脂肪组织的布朗宁是否导致代谢物信号分泌，并识别这些信号。将研究代谢物信号诱导邻近白色脂肪组织中的布朗宁以及通过血液向其他器官发出信号以调节全身代谢的能力。这项研究可能会发现米色细胞特异性代谢物信号，具有抗肥胖特性，并提供新的抗糖尿病疗法。示例项目2：食物成分可以对健康的广泛方面产生深远的影响，包括肠道功能，血糖控制和我们的思考能力。小麦和其他粮食作物含有天然存在的化合物，称为酚类，它可能具有抗氧化作用，可以减少已知在癌症和衰老中重要的DNA的细胞损伤。它们还可以改善肠道功能。该项目将使用LC-MS来测量抗氧化剂酚和肠道功能模型中的微量营养素，以了解这些抗氧化剂酚从食物中吸收的容易程度，确定改善其吸收的方法，并测量在酚存在下肠道对其他微量营养素的吸收，以确定它们如何影响肠道营养素的吸收。示例项目3：食物污染物和毒素是人类健康的主要风险，对低收入国家的弱势群体影响特别大。一组特殊的毒素被称为霉菌毒素，来自真菌，可以污染玉米和小麦等粮食作物，并与儿童生长发育迟缓和癌症的发展有关。该项目将使用所要求的LC-MS来测量非洲人群中的毒素水平和毒素暴露标志物，以了解不同作物、储存条件和地理位置的污染分布模式，并评估减少非洲霉菌毒素风险的干预措施的有效性。因此，为全球食品工业的安全和保障做出贡献。示例项目4：暴露于空气中交通微粒形式的环境污染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。

项目成果

Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle.

• DOI: 10.1038/s41467-022-29363-9
• 发表时间: 2022-04-01
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: McNally BD;Ashley DF;Hänschke L;Daou HN;Watt NT;Murfitt SA;MacCannell ADV;Whitehead A;Bowen TS;Sanders FWB;Vacca M;Witte KK;Davies GR;Bauer R;Griffin JL;Roberts LD
• 通讯作者: Roberts LD

Ice-Age Climate Adaptations Trap the Alpine Marmot in a State of Low Genetic Diversity

• DOI: 10.1016/j.cub.2019.04.020
• 发表时间: 2019-05-20
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Gossmann, Toni I.;Shanmugasundram, Achchuthan;Ralser, Markus
• 通讯作者: Ralser, Markus

Lipokines from browning adipose tissue are interorgan signals regulating adipose tissue, skeletal muscle and systemic metabolism to resist obesity

来自褐变脂肪组织的脂质因子是调节脂肪组织、骨骼肌和全身代谢以抵抗肥胖的器官间信号

• 发表时间: 2022
• 期刊: ACTA PHYSIOLOGICA
• 影响因子: 6.3
• 作者: Moran A.

Paracrine role for endothelial IGF-1 receptor in white adipocyte beiging

白色脂肪细胞内皮 IGF-1 受体的旁分泌作用

• DOI: 10.1101/2021.12.01.470734
• 发表时间: 2021
• 作者: Haywood N

The exercise-mediated metabokine Beta-aminoisobutyric acid is an exercise mimetic driving skeletal muscle metabolic and functional adaptation

运动介导的代谢因子β-氨基异丁酸是一种驱动骨骼肌代谢和功能适应的运动模拟物

• DOI: 10.1152/physiol.2023.38.s1.5786418
• 发表时间: 2023
• 期刊: Physiology
• 影响因子: 8.4
• 作者: Daou H