Multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) is a well-developed technology for global lipid analysis, which identifies and quantifies individual lipid molecular species ...directly from lipid extracts of biological samples. By using this technology, we have revealed three marked changes of lipids in brain samples of subjects with mild cognitive impairment of Alzheimer's disease including sulfatides, ceramides, and plasmalogens. Further studies using MDMS-SL lead us to the identification of the potential biochemical mechanisms responsible for the altered lipids at the disease state, which are thoroughly discussed in this minireview. Specifically, in studies to identify the causes responsible for sulfatide depletion at the mild cognitive impairment stage of Alzheimer's disease, we have found that apolipoprotein E is associated with sulfatide transport and mediates sulfatide homeostasis in the nervous system through lipoprotein metabolism pathways and that alterations in apolipoprotein E-mediated sulfatide trafficking can lead to sulfatide depletion in the brain. Collectively, the results obtained from lipidomic analyses of brain samples provide important insights into the biochemical mechanisms underlying the pathogenesis of Alzheimer's disease.
For over a century, the importance of lipid metabolism in biology was recognized but difficult to mechanistically understand due to the lack of sensitive and robust technologies for identification ...and quantification of lipid molecular species. The enabling technological breakthroughs emerged in the 1980s with the development of soft ionization methods (Electrospray Ionization and Matrix Assisted Laser Desorption/Ionization) that could identify and quantify intact individual lipid molecular species. These soft ionization technologies laid the foundations for what was to be later named the field of lipidomics. Further innovative advances in multistage fragmentation, dramatic improvements in resolution and mass accuracy, and multiplexed sample analysis fueled the early growth of lipidomics through the early 1990s. The field exponentially grew through the use of a variety of strategic approaches, which included direct infusion, chromatographic separation, and charge-switch derivatization, which facilitated access to the low abundance species of the lipidome. In this Thematic Review, we provide a broad perspective of the foundations, enabling advances, and predicted future directions of growth of the lipidomics field.
Triglyceride (TG) is a class of neutral lipids, which functions as an energy storage depot and is important for cellular growth, metabolism, and function. The composition and content of TG molecular ...species are crucial factors for nutritional aspects in food chemistry and are directly associated with several diseases, including atherosclerosis, diabetes, obesity, stroke, etc. As a result of the complexities of aliphatic moieties and their different connections/locations to the glycerol backbone in TG molecules, accurate identification of individual TG molecular species and quantitative assessment of TG composition and content are particularly challenging, even at the current stage of lipidomics development. Herein, methods developed for analysis of TG species, such as liquid chromatography–mass spectrometry with a variety of columns and different mass spectrometric techniques, shotgun lipidomics approaches, and ion-mobility-based analysis, are reviewed. Moreover, the potential limitations of the methods are discussed. It is our sincere hope that the overviews and discussions can provide some insights for researchers to select an appropriate approach for TG analysis and can serve as the basis for those who would like to establish a methodology for TG analysis or develop a new method when novel tools become available. Biologically accurate analysis of TG species with an enabling method should lead us toward improving the nutritional quality, revealing the effects of TG on diseases, and uncovering the underlying biochemical mechanisms related to these diseases.
Shotgun lipidomics is a rapidly developing technology, which identifies and quantifies individual lipid molecular species directly from lipid extracts of biological samples. Alterations in lipid ...molecular species in the brain induced by neurodegenerative diseases, such as Alzheimer's disease (AD) could provide fundamental clues to disease pathogenesis. To date, the cause(s) leading to AD pathogenesis are still unknown and apolipoprotein E (apoE) allele 4 is the only known major risk factor for this devastating disease. By utilizing shotgun lipidomics, we have recently shown that a substantial and specific depletion of sulfatide (a class of specialized myelin sphingolipids) is present in postmortem brains from subjects at the earliest clinically recognizable stage of AD. In subsequent studies to identify the biochemical mechanisms underlying sulfatide depletion at this very mild stage of AD, we have found that apoE is associated with sulfatide transport and mediates sulfatide homeostasis in the nervous system through lipoprotein metabolism pathways and that alterations in apoE-mediated sulfatide trafficking can lead to sulfatide depletion in the brain. Thus, a working model related to the potential biochemical mechanisms underlying sulfatide depletion in AD can be derived based on these results. Collectively, the results obtained from lipidomic analyses of brain samples provide important insights into the biochemical mechanisms underlying AD pathogenesis.
The essence of shotgun lipidomics is to maintain consistency of the chemical environment of lipid samples during mass spectrometry acquisition. This strategy is suitable for large-scale quantitative ...analysis. This strategy also allows sufficient time to collect data to improve the signal-to-noise ratio. The initial approach of shotgun lipidomics was the electrospray ionization (ESI)-based direct infusion mass spectrometry strategy. With development of mass spectrometry for small molecules, shotgun lipidomics methods have been extended to matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) and ambient mass spectrometry, including MS imaging methods. Furthermore, the object of analysis has extended from organ and body fluid levels to tissue and cell levels with technological developments. In this article, we summarize the status and technical challenges of shotgun lipidomics at different resolution of measurements from the mass spectrometry perspective.
•Summary of the essence and extension of shotgun lipidomics.•Introduction of the current state of shotgun lipidomics at different scales.•Description of the trend of mass spectrometric technologies for shotgun lipidomics at different scales.
Many thousands of lipid species exist and their metabolism is interwoven via numerous pathways and networks. These networks can also change in response to cellular environment alterations, such as ...exercise or development of a disease. Measuring such alterations and understanding the pathways involved is crucial to fully understand cellular metabolism. Such demands have catalysed the emergence of lipidomics, which enables the large-scale study of lipids using the principles of analytical chemistry. Mass spectrometry, largely due to its analytical power and rapid development of new instruments and techniques, has been widely used in lipidomics and greatly accelerated advances in the field. This Review provides an introduction to lipidomics and describes some common, but important, cellular metabolic networks that can aid our understanding of metabolic pathways. Some representative applications of lipidomics for studying lipid metabolism and metabolic diseases are highlighted, as well as future applications for the use of lipidomics in studying metabolic pathways.
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