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“…Attention should be given to the choice of internal standards 48 (which are typically deuterated themselves), and efforts are underway to expand methods for the development of lipidomic standards 49 . A comprehensive paper on the accurate quantitation of lipids has been published by Han and colleagues 50 , while Satapati et al recently reviewed the advantages of isotope-labeled flux measurements in preclinical studies, with particular emphasis on lipid tracing 51 . Continued advances in analytical capabilities will support the development of precision medicine strategies, which is currently one focus of the NIH ( https://acd.od.nih.gov/working-groups/pmi.html ).…”
Section: Research Needs To Support the Integration Of Isotopes In Pre...mentioning
Over the past 70 years, the study of lipid metabolism has led to important discoveries in identifying the underlying mechanisms of chronic diseases. Advances in the use of stable isotopes and mass spectrometry in humans have expanded our knowledge of target molecules that contribute to pathologies and lipid metabolic pathways. These advances have been leveraged within two research paths, leading to the ability (1) to quantitate lipid flux to understand the fundamentals of human physiology and pathology and (2) to perform untargeted analyses of human blood and tissues derived from a single timepoint to identify lipidomic patterns that predict disease. This review describes the physiological and analytical parameters that influence these measurements and how these issues will propel the coming together of the two fields of metabolic tracing and lipidomics. The potential of data science to advance these fields is also discussed. Future developments are needed to increase the precision of lipid measurements in human samples, leading to discoveries in how individuals vary in their production, storage, and use of lipids. New techniques are critical to support clinical strategies to prevent disease and to identify mechanisms by which treatments confer health benefits with the overall goal of reducing the burden of human disease.
“…Attention should be given to the choice of internal standards 48 (which are typically deuterated themselves), and efforts are underway to expand methods for the development of lipidomic standards 49 . A comprehensive paper on the accurate quantitation of lipids has been published by Han and colleagues 50 , while Satapati et al recently reviewed the advantages of isotope-labeled flux measurements in preclinical studies, with particular emphasis on lipid tracing 51 . Continued advances in analytical capabilities will support the development of precision medicine strategies, which is currently one focus of the NIH ( https://acd.od.nih.gov/working-groups/pmi.html ).…”
Section: Research Needs To Support the Integration Of Isotopes In Pre...mentioning
Over the past 70 years, the study of lipid metabolism has led to important discoveries in identifying the underlying mechanisms of chronic diseases. Advances in the use of stable isotopes and mass spectrometry in humans have expanded our knowledge of target molecules that contribute to pathologies and lipid metabolic pathways. These advances have been leveraged within two research paths, leading to the ability (1) to quantitate lipid flux to understand the fundamentals of human physiology and pathology and (2) to perform untargeted analyses of human blood and tissues derived from a single timepoint to identify lipidomic patterns that predict disease. This review describes the physiological and analytical parameters that influence these measurements and how these issues will propel the coming together of the two fields of metabolic tracing and lipidomics. The potential of data science to advance these fields is also discussed. Future developments are needed to increase the precision of lipid measurements in human samples, leading to discoveries in how individuals vary in their production, storage, and use of lipids. New techniques are critical to support clinical strategies to prevent disease and to identify mechanisms by which treatments confer health benefits with the overall goal of reducing the burden of human disease.
“…The development of lipidomics most significantly depended on new developments in mass spectrometry, which caused me to transition entirely from acquiring NMR spectrometers to mass spectrometers (MS). Han and Gross [19] have recently reviewed the evolution of mass spectrometry technologies in the service of lipidomics during this period.…”
Section: Organizational Leadership Of the Lipid Maps Initiativementioning
My laboratoryâs research on lipids has focused on phospholipases and lipidomics and in many ways has evolved in parallel to the evolution of the lipid field over the past half century. I have reviewed our research elsewhere. Herein, I describe the âside storiesâ or âouttakesâ that parallel the main story that focuses on our laboratoryâs research. I will emphasize the importance of community activities and describe how I came to initiate and lead the international effort on the Lipid Metabolites and Pathways Strategy (LIPID MAPS). Several of these side activities had a significant effect on discoveries in my laboratory research and its evolution as well as contributing significantly to the development of the LIPID MAPS initiative. These included experience and influences from serving as Editor-in-Chief of the Journal of Lipid Research and Chair and President of the Keystone Symposia on Cell and Molecular Biology as well as other experiences in organizing lipid conferences, teaching on lipid structure and mechanism, and earlier formative administrative and leadership experiences. The relevant influences are summarized herein.
“…At present, metabolomics has been used to study metabolic diseases, including diabetes, obesity, and metabolic syndrome [ 26 â 28 ]. As an important branch of metabolomics, lipidomics focus to measure the number of lipids and allow the analysis of the alternations of lipid metabolism by determining the characteristics of lipid compositions at different stages of disease progression [ 29 , 30 ]. Since NAFLD is highly related to lipid metabolism, lipidomic analysis of EVs might provide unique insights for exploring the pathological mechanism of the disease, especially the underlying etiology in developing NASH from NAFL.…”
Background and Aims
Non-alcoholic fatty liver disease (NAFLD) is a usual chronic liver disease and lacks non-invasive biomarkers for the clinical diagnosis and prognosis. Extracellular vesicles (EVs), a group of heterogeneous small membrane-bound vesicles, carry proteins and nucleic acids as promising biomarkers for clinical applications, but it has not been well explored on their lipid compositions related to NAFLD studies. Here, we investigate the lipid molecular function of urinary EVs and their potential as biomarkers for non-alcoholic steatohepatitis (NASH) detection.
Methods
This work includes 43 patients with non-alcoholic fatty liver (NAFL) and 40 patients with NASH. The EVs of urine were isolated and purified using the EXODUS method. The EV lipidomics was performed by LC-MS/MS. We then systematically compare the EV lipidomic profiles of NAFL and NASH patients and reveal the lipid signatures of NASH with the assistance of machine learning.
Results
By lipidomic profiling of urinary EVs, we identify 422 lipids mainly including sterol lipids, fatty acyl lipids, glycerides, glycerophospholipids, and sphingolipids. Via the machine learning and random forest modeling, we obtain a biomarker panel composed of 4 lipid molecules including FFA (18:0), LPC (22:6/0:0), FFA (18:1), and PI (16:0/18:1), that can distinguish NASH with an AUC of 92.3%. These lipid molecules are closely associated with the occurrence and development of NASH.
Conclusion
The lack of non-invasive means for diagnosing NASH causes increasing morbidity. We investigate the NAFLD biomarkers from the insights of urinary EVs, and systematically compare the EV lipidomic profiles of NAFL and NASH, which holds the promise to expand the current knowledge of disease pathogenesis and evaluate their role as non-invasive biomarkers for NASH diagnosis and progression.
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