Focusing on the practical applications, this user-oriented guide presents current technologies and strategies for systems-level lipid
analysis, going beyond basic research to concentrate on commercial uses of lipidomics in biomarker and diagnostic development, as well
as within pharmaceutical drug discovery and development. The editor and authors have experience of the most recent analytical instruments and techniques, allowing them to provide here first-hand practical experience for newcomers to the field. The first half of the book covers current methodologies, ranging from global to targeted lipidomics and shotgun approaches, while the second part discusses the role of lipidomics in biomedical and pharmaceutical research, covering such diverse fields as inflammation, metabolic syndrome, cardiovascular and neurological disease. Both small and large-scale, high-throughput approaches are discussed, resulting in an invaluable source for academic and industrial research and development.
Kim Ekroos currently heads the bioanalytics division at Zora Biosciences in Espoo (Finland). He holds a Ph.D. from the Technical University of Dresden (Germany) and has conducted research in the group of Professor Kai Simons and Dr. Andrej Shevchenko at the Max-Planck Institute of Molecular Cell Biology and Genetics in Dresden. Dr. Ekroos has also worked at the European Molecular Biology Laboratory in Heidelberg (Germany). He has made major contributions to the advancement of basic research on lipids and their study with advanced mass spectroscopy methods and software tools. In addition, he has pharmaceutical industry experience from Astra Zeneca where he spent three years successfully developing and utilizing high-throughput molecular lipidomics methods. Today he is focusing on applied molecular lipidomics for unscrambling the mechanistic details by which alterations in tissue-specific lipid metabolism are directly linked to the etiology of lipid-mediated disorders for the benefit of basic science, drug target and lipid biomarker discovery, and development of clinical diagnostics.
PREFACE LIPIDOMICS PERSPECTIVE: FROM MOLECULAR LIPIDOMICS TO VALIDATED CLINICAL DIAGNOSTICS Introduction Hierarchical Categorization of the Analytical Lipid Outputs The Type of Lipid Information Delivers Different Biological Knowledge Untying New Biological Evidences through Molecular Lipidomic Applications Molecular Lipidomics Approaches Clinical Diagnostics Current Roadblocks in Lipidomics Conclusions LIPIDS IN CELLS Introduction Basis of Cellular Lipid Distribution Lipid Distribution by Nonvesicular Routes Lipids in Different Cell Types Functional Implications of Membrane Lipid Composition Outlook: Collectives and Phase Separation HIGH-THROUGHPUT MOLECULAR LIPIDOMICS Introduction Lipid Diversity Function of Molecular Lipids Automated Sample Preparation Different Approaches to Molecular Lipidomics Data Processing and Evaluation Lipidomic Workflows Conclusions and Future Perspectives MULTIDIMENSIONAL MASS SPECTROMETRY-BASED SHOTGUN LIPIDOMICS Introduction Multidimensional Mass Spectrometry-Based Shotgun Lipidomics Application of Multidimensional Mass Spectrometry-Based Shotgun Lipidomics for Lipidomic Analysis Conclusions TARGETED LIPIDOMICS: SPHINGOLIPIDOMICS Introduction Sphingolipids Description and Nomenclature Sphingolipids Analysis via Targeted LC-MS/MS Applications of Sphingolipidomics in Biology and Disease Conclusions STRUCTURAL LIPIDOMICS Introduction Lipid Structure Structural Analysis of Lipids by Mass Spectrometry sn Position Double Bond Position Double Bond Stereochemistry Conclusions IMAGING LIPIDS IN TISSUES BY MATRIX-ASSISTED LASER DESORPTION/IONIZATION MASS SPECTROMETRY Introduction Sample Preparation Matrix Instrumentation Data Processing Conclusions LIPID INFORMATICS: FROM A MASS SPECTRUM TO INTERACTOMICS Introduction Lipid Nomenclature Basic Properties of Lipid Mass Spectrometric Data Data Processing Lipidomic Data Mining and Visualization Lipidomic Data Integration Conclusions and Future Perspectives LIPIDS IN HUMAN DISEASES Introduction Obesity Dyslipidemia Diabetes Cardiovascular Disorders Hereditary Sensory Neuropathy Neurodegeneration Cancer Lysosomal Storage Disorders Cystic Fibrosis Anti-Inflammatory Lipid Mediators Conclusions LIPIDOMICS IN LIPOPROTEIN BIOLOGY Introduction Metabolism of Lipoproteins Lipoproteinomics in Normolipidemic Subjects Altered Lipoproteinomics in Dyslipidemia Conclusions MEDIATOR LIPIDOMICS IN INFLAMMATION RESEARCH Introduction PUFA-Derived Lipid Mediators: Formation and Action LC-ESI-MS/MS-Based Lipidomics Mediator Lipidomics in Inflammation and Resolution Conclusion and Future Perspective LIPIDOMICS FOR ELUCIDATION OF METABOLIC SYNDROME AND RELATED LIPID METABOLIC DISORDER Introduction Basic Strategy of Lipidomics for Elucidating Metabolic Changes of Lipids at the Level of their Molecular Species in Metabolic Syndrome and Related Diseases Analytical Systems by Mass Spectrometry in Lipidomics Lipidomic Data Processing u Analysis of Lipids as Markers of Metabolic Syndrome Direct Detection of Lipid Molecular Species in Specific Tissue Domains by Disease-Specific Changes Conclusions LIPIDOMICS IN ATHEROSCLEROTIC VASCULAR DISEASE Introduction Lipids and Atherosclerotic Vascular Disease Diagnostics and Treatment Conclusions LIPID METABOLISM IN NEURODEGENERATIVE DISEASES Introduction Parkinson?s Disease Conclusions THE TUMOR MITOCHONDRIAL LIPIDOME AND RESPIRATORY BIOENERGETIC INSUFFICIENCY Introduction Cardiolipin and Electron Transport Chain Abnormalities in Mouse Brain Tumor Mitochondria Complicating Influence of the in vitro Growth Environment on Cardiolipin Composition and Energy Metabolism Bioinformatic Methods to Interpret Alterations in the Mitochondrial Lipidome Conclusions LIPIDOMICS FOR PHARMACEUTICAL RESEARCH Introduction Biomarkers for Pharmaceutical Research Strategy for Biomarker Discovery Conclusions INDEX