脂质组学在毒理学研究中的应用

脂质作为细胞的主要组成部分,在细胞内物质运输、信号转导、细胞凋亡等多种生命活动中发挥重要作用。脂质组学通过对生物体内的脂质进行系统分析,从而了解其相互作用以及与其他生物分子之间的作用。主要介绍了脂质组学的研究方法,包括样品前处理方法、检测方法和仪器设备以及数据分析方法。同时,综述了脂质组学技术在神经毒性、肝脏毒性、免疫毒性以及内分泌干扰毒性中的研究进展,以期为研究化合物毒性作用机制提供思路和参考。最后,提出未来应利用脂质组学技术开展不同化合物的联合毒性作用研究,通过脂质组学筛选获得相关脂质生物标志物,为联合毒性作用的风险预警和相关毒性作用机制分析提供科学依据。     

脂质组学在医药研究中的应用

脂质组学是对整体脂质进行系统分析的一门新兴学科,通过比较不同生理状态下脂代谢网络的变化,进而识别代谢调控中关键的脂生物标志物,最终揭示脂质在各种生命活动中的作用机制。电喷雾电离-质谱技术是脂质组学领域中最核心的研究手段,目前已能对各种脂质尤其是磷脂进行高分辨率、高灵敏度、高通量的分析。随着质谱技术的进步,脂质组学在疾病脂生物标志物的识别、疾病诊断、药物靶点及先导化合物的发现和药物作用机制的研究等方面已展现出广泛的应用前景。     

脂质组学研究方法及其应用

脂质不仅是生物膜的骨架成分和能量贮存物质, 越来越多的证据表明, 脂质也参与细胞的许多重要功能。脂质组学是代谢组学的一个重要分支, 主要研究生物体内所有的脂质分子的特性以及它们在蛋白质表达和基因调控过程中的作用。脂质组学是依赖技术驱动的科学。近年来, 随着人们对脂质研究的重视, 脂质组学研究方法和策略有了突破性进展, 在动物上开发出的脂质组学分析方法已经扩展应用到植物上。该文重点介绍脂质组学的研究方法及其应用, 以期推动脂质组学,特别是植物脂质组学的进一步发展。     

脂质组学研究方法及其应用

脂质不仅是生物膜的骨架成分和能量贮存物质,越来越多的证据表明,脂质也参与细胞的许多重要功能。脂质组学是代谢组学的一个重要分支,主要研究生物体内所有的脂质分子的特性以及它们在蛋白质表达和基因调控过程中的作用。脂质组学是依赖技术驱动的科学。近年来,随着人们对脂质研究的重视,脂质组学研究方法和策略有了突破性进展,在动物上开发出的脂质组学分析方法已经扩展应用到植物上。该文重点介绍脂质组学的研究方法及其应用,以期推动脂质组学,特别是植物脂质组学的进一步发展。     

代谢组学技术及其在毒理学研究领域中的应用

代谢组学是近几年发展起来的对某一生物或细胞所有低分子量代谢产物进行定性和定量分析的一门新学科,其研究对象主要是生物体液,研究手段主要是核磁共振和质谱。简要综述了代谢组学的概念、代谢组学在毒理学研究领域中的应用、当前代谢组学研究中存在的问题及今后的发展趋势,并探讨了代谢组学在研究毒物作用机制、药物的临床前安全性评价、确定毒物作用靶器官及器官特异性新的生物标志物中的实际应用。     

脂质组学研究进展

综述了脂质组学的研究现状和发展趋势.脂质组学是对生物体、组织或细胞中的脂质以及与其相互作用的分子进行系统分析的一门新兴学科.脂质具有多种重要的生物功能,脂质代谢异常可引发诸多人类疾病,包括糖尿病、肥胖症、癌症以及神经退行性疾病等.目前,脂质组学研究已成为一个前景广阔的热门领域,并广泛地应用到包括药物研发、分子生理学、分子病理学、功能基因组学、营养学以及环境与健康等重要领域.     

植物脂质应答逆境胁迫生理功能的研究进展

脂质是生命有机体中一类重要的化合物,可以参与并调节多种生命活动,并且在植物应答非生物胁迫(盐胁迫、干旱胁迫和温度胁迫等)过程中发挥着重要生理功能。但长期以来,对于脂质的研究多集中于动物细胞和医学领域,却疏于关注植物研究领域。借助于"组"学思想和生物技术的快速发展,脂质组学由于可以深层次、全面地揭示脂质的组分与功能,近年来备受关注。基于此,文中通过对脂质的功能与分类、脂质组学技术进展、植物脂质响应干旱胁迫、盐胁迫和温度胁迫生理功能进展等的国内外现有研究进行了归纳与总结,并提出了不足与展望,为探索脂质在植物抗逆过程的生理功能和脂质组学等领域深入研究提供一定的基础。     

莱茵衣藻中脂质代谢过程研究进展

微藻中脂质代谢产生的化合物,可用于生物燃料、营养品和生物药品的生产,因此具有重要的经济价值。脂质代谢贯穿微藻的全部生命过程,对微藻的生长发育和应对外界胁迫都具有重要意义。微藻与研究较清楚的真菌和陆地植物在脂质代谢过程方面具有相似性。当然,随着微藻脂质代谢相关功能基因逐渐被鉴定,人们发现微藻的脂质代谢也具有区别真菌和陆地植物的独特性,因此针对微藻脂质代谢过程的分析具有重要意义。莱茵衣藻是研究脂质代谢过程的模式生物,已经通过基因组、转录组、蛋白质组和代谢组等方法,对其质体、内质网和过氧化物酶体中进行的脂质合成和分解过程进行了研究。本文总结了近年来莱茵衣藻质体、内质网和过氧化物酶体中脂质代谢过程的研究成果,并进行综合阐述。     

多组学分析在昆虫滞育中的应用

组学技术将生物的相关问题分别展现在基因、蛋白质和代谢物等不同层次水平上，已成为解读生命过程的重要工具。本文分别从转录组学、蛋白质组学、代谢组学以及组学间的联合应用等方面概括总结了组学技术在昆虫滞育研究中的应用情况，阐述了以转录组学、蛋白质组学和代谢组学为代表的多组学技术在昆虫滞育调控分子机制中取得的重要成果，并针对当前研究现状，对昆虫滞育中组学技术应用的前景和局限性进行了总结和展望，以期为昆虫滞育调控分子机制的研究提供参考依据。     

生物质谱分析法在脂质组学的应用

脂质与许多慢性病(如糖尿病、高血压)和精神系统疾病(如阿尔茨海默病)等有关。脂质组学是以现代生物技术为手段,对生物体中的全脂质进行定性和定量的一门新兴学科。目前,生物质谱分析法是对脂质谱进行分析和定量的最有效方法,国内对脂质组学的系统研究还比较匮乏。综述脂质组学的概念与分类,探究不同的生物样品前处理方法,系统介绍近几年国际上生物质谱分析法在脂质组学的应用,并对脂质组学的发展趋势进行展望。     

Lipidomics as a Principal Tool for Advancing Biomedical Research

Lipidomics,which targets at the construction of a comprehensive map of lipidome comprising the entire lipid pool within a cell or tissue,is currently emerging as an independent discipline at the interf...     

Surface analysis of lipids by mass spectrometry: More than just imaging

Mass spectrometry is now an indispensable tool for lipid analysis and is arguably the driving force in the renaissance of lipid research. In its various forms, mass spectrometry is uniquely capable of resolving the extensive compositional and structural diversity of lipids in biological systems. Furthermore, it provides the ability to accurately quantify molecular-level changes in lipid populations associated with changes in metabolism and environment; bringing lipid science to the “omics” age. The recent explosion of mass spectrometry-based surface analysis techniques is fuelling further expansion of the lipidomics field. This is evidenced by the numerous papers published on the subject of mass spectrometric imaging of lipids in recent years. While imaging mass spectrometry provides new and exciting possibilities, it is but one of the many opportunities direct surface analysis offers the lipid researcher. In this review we describe the current state-of-the-art in the direct surface analysis of lipids with a focus on tissue sections, intact cells and thin-layer chromatography substrates. The suitability of these different approaches towards analysis of the major lipid classes along with their current and potential applications in the field of lipid analysis are evaluated.     

Lipidomic profiling of model organisms and the world's major pathogens

Lipidomics is a subspecialty of metabolomics that focuses on water insoluble metabolites that form membrane barriers. Most lipidomic databases catalog lipids from common model organisms, like humans or Escherichia coli. However, model organisms' lipid profiles show surprisingly little overlap with those of specialized pathogens, creating the need for organism-specific lipidomic databases. Here we review rapid progress in lipidomic platform development with regard to chromatography, detection and bioinformatics. We emphasize new methods of comparative lipidomics, which use aligned datasets to identify lipids changed after introducing a biological variable. These new methods provide an unprecedented ability to broadly and quantitatively describe lipidic change during biological processes and identify changed lipids with low error rates.     

Lipidomics analysis in drug discovery and development

Despite being a relatively new addition to the Omics' landscape, lipidomics is increasingly being recognized as an important tool for the identification of druggable targets and biochemical markers. In this review we present recent advances of lipid analysis in drug discovery and development. We cover current state of the art technologies which are constantly evolving to meet demands in terms of sensitivity and selectivity. A careful selection of important examples is then provided, illustrating the versatility of lipidomics analysis in the drug discovery and development process. Integration of lipidomics with other omics’, stem-cell technologies, and metabolic flux analysis will open new avenues for deciphering pathophysiological mechanisms and the discovery of novel targets and biomarkers.     

Diurnal Regulation of Lipid Metabolism and Applications of Circadian Lipidomics

The circadian timing system plays a key role in orchestrating lipid metabolism. In concert with the solar cycle, the circadian system ensures that daily rhythms in lipid absorption, storage, and transport are temporally coordinated with rest-activity and feeding cycles. At the cellular level, genes involved in lipid synthesis and fatty acid oxidation are rhythmically activated and repressed by core clock proteins in a tissue-specific manner. Consequently, loss of clock gene function or misalignment of circadian rhythms with feeding cycles （e.g., in shift work） results in impaired lipid homeostasis. Herein, we review recent progress in circadian rhythms research using lipidomics, i.e., large-scale profiling of lipid metabolites, to characterize circadian-regulated lipid pathways in mammals. In mice, novel regulatory circuits involved in fatty acid metabolism have been identified in adipose tissue, liver, and muscle. Extensive diversity in circadian regulation of plasma lipids has also been revealed in humans using lipidomics and other metabolomics approaches. In future studies, lipidomics platforms will be increasingly used to better understand the effects of genetic variation, shift work, food intake, and drugs on circadian-regulated lipid pathways and metabolic health.     

Lipidomic analysis of epidermal lipids: a tool to predict progression of inflammatory skin disease in humans

Introduction: Lipidomics is the large-scale profiling and characterization of lipid species in a biological system using mass spectrometry. The skin barrier is mainly comprised of corneocytes and a lipid-enriched extracellular matrix. The major skin lipids are ceramides, cholesterol and free fatty acids (FFA). Lipid compositions are altered in inflammatory skin disorders with disrupted skin barrier such as atopic dermatitis (AD).

Areas covered: Here we discuss some of the recent applications of lipidomics in human skin biology and in inflammatory skin diseases such as AD, psoriasis and Netherton syndrome. We also review applications of lipidomics in human skin equivalent and in pre-clinical animal models of skin diseases to gain insight into the pathogenesis of the skin disease.

Expert commentary: Skin lipidomics analysis could be a fast, reliable and noninvasive tool to characterize the skin lipid profile and to monitor the progression of inflammatory skin diseases such as AD.     

Comprehensive lipidomics in apoM-/- mice reveals an overall state of metabolic distress and attenuated hepatic lipid secretion into the circulation

Apolipoprotein M (apoM) participates in both high-density lipoprotein and cholesterol metabolism. Little is known about how apoM affects lipid composition of the liver and serum. In this study, we systemically investigated the effects of apoM on liver and plasma lipidomes and how apoM participates in lipid cycling, via apoM knockout in mice and the human SMMC-7721 cell line. We used integrated mass spectrometry-based lipidomics approaches to semiquantify more than 600 lipid species from various lipid classes, which include free fatty acids, glycerolipids, phospholipids, sphingolipids, glycosphingolipids, cholesterol, and cholesteryl esters (CEs), in apoM^-/- mouse. Hepatic accumulation of neutral lipids, including CEs, triacylglycerols, and diacylglycerols, was observed in apoM^-/- mice; while serum lipidomic analyses showed that, in contrast to the liver, the overall levels of CEs and saturated/monounsaturated fatty acids were markedly diminished. Furthermore, the level of ApoB-100 was dramatically increased in the liver, whereas significant reductions in both ApoB-100 and low-density lipoprotein (LDL) cholesterol were observed in the serum of apoM^-/- mice, which indicated attenuated hepatic LDL secretion into the circulation. Lipid profiles and proinflammatory cytokine levels indicated that apoM^-/- leads to hepatic steatosis and an overall state of metabolic distress. Taken together, these results revealed that apoM knockout leads to hepatic steatosis, impaired lipid secretion, and an overall state of metabolic distress.     

Strategies to Improve/Eliminate the Limitations in Shotgun Lipidomics

Direct infusion‐based shotgun lipidomics is one of the most powerful and useful tools in comprehensive analysis of lipid species from lipid extracts of various biological samples with high accuracy/precision. However, despite many advantages, the classical shotgun lipidomics suffers some general dogmas of limitations, such as ion suppression, ambiguous identification of isobaric/isomeric lipid species, and ion source–generated artifacts, restraining the applications in analysis of low‐abundance lipid species, particularly those less ionizable or isomers that yield almost identical fragmentation patterns. This article reviews the strategies (such as modifier addition, prefractionation, chemical derivatization, charge feature utilization) that have been employed to improve/eliminate these limitations in modern shotgun lipidomics approaches (e.g., high mass resolution mass spectrometry–based and multidimensional mass spectrometry–based shotgun lipidomics). Therefore, with the enhancement of these strategies for shotgun lipidomics, comprehensive analysis of lipid species including isomeric/isobaric species is achieved in a more accurate and effective manner, greatly substantiating the aberrant lipid metabolism, signaling trafficking, and homeostasis under pathological conditions.     

Novel advances in shotgun lipidomics for biology and medicine

The field of lipidomics, as coined in 2003, has made profound advances and been rapidly expanded. The mass spectrometry-based strategies of this analytical methodology-oriented research discipline for lipid analysis are largely fallen into three categories: direct infusion-based shotgun lipidomics, liquid chromatography-mass spectrometry-based platforms, and matrix-assisted laser desorption/ionization mass spectrometry-based approaches (particularly in imagining lipid distribution in tissues or cells). This review focuses on shotgun lipidomics. After briefly introducing its fundamentals, the major materials of this article cover its recent advances. These include the novel methods of lipid extraction, novel shotgun lipidomics strategies for identification and quantification of previously hardly accessible lipid classes and molecular species including isomers, and novel tools for processing and interpretation of lipidomics data. Representative applications of advanced shotgun lipidomics for biological and biomedical research are also presented in this review. We believe that with these novel advances in shotgun lipidomics, this approach for lipid analysis should become more comprehensive and high throughput, thereby greatly accelerating the lipidomics field to substantiate the aberrant lipid metabolism, signaling, trafficking, and homeostasis under pathological conditions and their underpinning biochemical mechanisms.