Diet induced obesity and adipose tissue: respiratory function, subcellular structure and lipid composition.

饮食引起的肥胖和脂肪组织：呼吸功能、亚细胞结构和脂质成分。

• 批准号: 2274907
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2274907
• 关键词: Diet; induced; obesity; adipose; tissue

Rotation 1 - October - December 2019Ion Mobility as a tool for lipidomics to understand lipid remodelling in obesityPhd: Lipids are of fundamental importance to the cell, acting as major components of cell membranes, important energy storage sources, signalling molecules and precursors for a wide range of biomolecules. Thus, it is of fundamental importance for many biological systems to be able to measure the diverse range of lipids that make up the cellular lipidome. However, a major challenge of the mass spectrometry of complex lipid mixtures from biological material is the separation of isobaric compounds, which often have similar chromatographic properties limiting the use of liquid chromatography for separation, while fragmentation data can be inconclusive in determining chemical structure. Ion mobility allows the separation of isobaric ions based on their mobilities through an inert gas, with mobility correlated to the collisional cross sections (CCSs) of molecules. We have been applying this approach in conjunction with high resolution mass spectrometry and chromatography to maximise the resolving power of different lipid classes. As part of the method development we have also developed a data pipeline within the software package KNIME to process the three dimensional data that is produced by the workflow as well as developing an in-house database based on mass-to-charge (m/z) ratios, retention times, MS/MS spectra, and CCS values of non-labelled phospholipid and fatty acid standards. This studentship will use these developments in ion mobility based lipidomics to study diet induced obesity in a rodent model. Specifically, we will look at how diets high in saturated fats affect the composition of cell membranes within key tissues across the body, using ion mobility to increase our coverage of the lipidome. We will also investigate whether CCS values can be used to model changes in cell membrane composition and fluidity as is thought to occur when dietary saturated fats begin to displace mono- and polyunsaturated fats in cell membranes. We will combine these measurements with functional outcomes and assess mitochondrial function using oxygen electrodes, as well as lipid-induced endoplasmic reticulum and mitochondrial stress.

旋转 1 - 十月 - 十二月 2019离子淌度作为脂质组学的工具，以了解肥胖中的脂质重塑博士：脂质对细胞至关重要，是细胞膜的主要成分、重要的能量存储来源、信号分子和多种生物分子的前体。因此，对于许多生物系统来说，能够测量构成细胞脂质组的各种脂质是至关重要的。然而，对生物材料中的复杂脂质混合物进行质谱分析的一个主要挑战是同量异位化合物的分离，这些化合物通常具有相似的色谱特性，限制了液相色谱法进行分离的使用，而碎片数据在确定化学结构方面可能并不确定。离子淌度允许根据同量异位离子在惰性气体中的迁移率进行分离，迁移率与分子的碰撞截面 (CCS) 相关。我们一直将这种方法与高分辨率质谱和色谱法结合应用，以最大限度地提高不同脂质类别的分辨能力。作为方法开发的一部分，我们还在软件包 KNIME 中开发了一个数据管道，用于处理工作流程生成的三维数据，并根据质荷 (m/z) 比、保留时间、MS/MS 谱图以及非标记磷脂和脂肪酸标准品的 CCS 值开发内部数据库。该奖学金将利用基于离子淌度的脂质组学的这些进展来研究啮齿动物模型中饮食引起的肥胖。具体来说，我们将研究饱和脂肪含量高的饮食如何影响全身关键组织内细胞膜的组成，利用离子淌度来增加脂质组的覆盖范围。我们还将研究 CCS 值是否可以用于模拟细胞膜组成和流动性的变化，正如人们认为的那样，当膳食饱和脂肪开始取代细胞膜中的单不饱和脂肪和多不饱和脂肪时就会发生这种变化。我们将把这些测量结果与功能结果结合起来，并使用氧电极评估线粒体功能，以及脂质诱导的内质网和线粒体应激。