Lipidomics for Studying Metabolism

Lipids are a diverse group of molecules that serve essential roles in energy storage, cellular structure, signaling pathways, and numerous physiological processes. Lipidomics aims to characterize the entire lipid profile of a biological sample, providing insights into the intricate interactions between lipids and their roles in cellular metabolism. [What is Lipidomics? Check out your answer via a few Q&As here]

To conclude, lipidomics offers a powerful toolset for studying metabolism by unraveling the complexity of lipid molecules and their involvement in various cellular processes. Some key aspects of lipidomics for studying metabolism:

  1. Lipid Diversity: Lipids encompass a vast array of molecules, including fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and many more. Each lipid class has specific functions in cellular metabolism and signaling pathways.
  2. Metabolic Pathways: Lipidomics helps uncover metabolic pathways involving lipids. By analyzing the levels and changes of different lipid species, researchers can gain insights into how lipids contribute to metabolic processes.
  3. Disease Biomarkers: Lipidomics plays a crucial role in identifying lipid-based biomarkers associated with metabolic disorders, such as obesity, diabetes, cardiovascular diseases, and neurodegenerative conditions. Altered lipid profiles can indicate disease progression or response to treatment.
  4. Drug Development: Lipidomics contributes to drug development by elucidating how drugs interact with lipid pathways and affect lipid profiles. This knowledge is crucial for understanding drug mechanisms of action, potential side effects, and optimizing therapeutic strategies.
  5. Quantitative Analysis: Mass spectrometry is a commonly used technique for lipidomics, enabling the identification and quantification of numerous lipid molecules within a sample.
  6. Multi-Omics Integration: Integrating lipidomics data with other omics data, such as metabolomics and proteomics, provides a more holistic view of cellular processes and their regulation.

Assays and Publications

Targeted Lipidomics
International Ring Trial of a High Resolution Targeted Metabolomics and Lipidomics Platform for Serum and Plasma Analysis

The comparability of quantitative metabolomics measurements in large human cohorts is a challenge. To address this, a study engaged 14 laboratories to analyze diverse blood specimens using a standardized protocol and the Biocrates AbsoluteIDQ p400HR kit, enabling the quantification of up to 408 metabolites, spanning 11 common metabolite classes. The study’s outcomes offer guidelines for optimal practices concerning system suitability, quality control, and calibration. It demonstrates that when using suitable controls, high-resolution metabolomics can deliver accurate and highly precise results consistently across different laboratories. Dr. Wishart’s group was one of the main collaborators for this study.

Comprehensive Lipid Profiling by Multisegment Injection–Nonaqueous Capillary Electrophoresis–Mass Spectrometry: Expanding Coverage Beyond Hydrophilic Metabolites

This book chapter is coauthored by Dr. Britz-McKibbin, reveals that over the past seven decades, advancements in analytical instrumentation, particularly separation science and mass spectrometry (MS), have driven the evolution of methods for quantitative lipid profiling. Nonaqueous capillary electrophoresis (CE) has emerged as an effective microseparation platform, capable of resolving water-insoluble compounds using a conductive electrolyte within an organic solvent or solvent mixture with a small water fraction. In 2013, the authors introduced a high-throughput metabolite analysis method called multisegment injection–CE–MS, which involves injecting multiple samples sequentially within a single run, enhancing efficiency and throughput.

Dr. Philip Britz-McKibbin laboratory at McMaster University

TMIC offers a few targeted lipidomics analyses:

  • Sphingolipid Synthesis Metabolism. Quantification of sphingolipid biosynthesis phosphate intermediates, sphinganines, ceramides, sphingomyelins, sulfatides, cerebrosides, and gangliosides by UPLC-MRM/MS.
  • Mevalonate Pathway and Isoprenoids/Cholesterol Synthesis. Detection and quantitation of isoprenyl phosphate intermediates, isoprenoids (ubiquinones, dolichols, vitamin K2 and squalene, etc.), cholesterol and other sterols by UPLC-MRM/MS and UPLC-FTMS. It includes 17 lipids and lipid-like molecules.
  • NMR Analysis. Targeted analysis of water soluble metabolite classes including amino acids, sugars, alcohols, organic acids, amines, TCA cycle intermediates, and short chain fatty acids. This assay also targets some of fatty acyls, glycerophospholipids, prenol lipids, steroids and steroid derivatives.
  • Biocrates p400. Targeted analysis of biogenic amines, amino acids, acylcarnitines, and 7 lipid classes using the Biocrates p400 kit. This is the method published in the paper above, International Ring Trial of a High Resolution Targeted Metabolomics and Lipidomics Platform for Serum and Plasma Analysis.
  • Targeted Lipidomics. Extraction, separation, and quantification of 4 neutral lipid classes and 9 phospholipid classes using GC-FAMES-MS.
Untargeted Lipidomics
Development of a NanoLC-MS workflow for high-sensitivity global lipidomic analysis

Dr. Li’s group has consistently dedicated significant work to advance the field of lipidomics and its associated technologies. Lipidomics focuses on the comprehensive analysis of lipids and their interactions with other molecules. Lipidomics involves in-depth exploration of lipids and their interactions with other molecules. Analyzing complex lipid compositions in small or scarce biological samples demands highly sensitive methods. While NanoLC-MS provides exceptional sensitivity, it’s technically more demanding than traditional LC-MS, necessitating meticulous care and maintenance. This work describes the development and optimization of a nanoLC-MS method for routine analysis of the lipidome of small volumes of biological samples. 

Comprehensive Serum Lipidomics for Detecting Incipient Dementia in Parkinson’s Disease

Another focus on Li’s group is the application of lipidomics in clinical applications, especially on the neurodegenerative diseases. This study addresses the challenge of unbiased untargeted lipidomics for comprehensive lipid analysis. The focus is on Parkinson’s disease (PD), a neurodegenerative disorder that can lead to dementia. By analyzing serum samples from PD patients and healthy controls, two biomarker panels were developed: one distinguishing PD patients from controls, and another identifying PD patients at risk of transitioning to dementia. These panels hold promise for early detection and interventions in prodromal PD dementia, with discussions on changed lipid biochemistry within the context of neurological pathologies and the potential for future larger sample studies.

Nontargeted Serum Lipid Profiling of Nonalcoholic Steatohepatitis by Multisegment Injection–Nonaqueous Capillary Electrophoresis–Mass Spectrometry: A Multiplexed Separation Platform for Resolving Ionic Lipids

In response to the intricate chemical structures and diverse properties of lipids, a new approach for comprehensive lipid profiling is introduced by Dr Britz-McKibbin’s team. The method involves a robust data workflow using multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry (MSI-NACE-MS) to selectively identify lipid features in serum ether extracts. This approach employs an iterative three-stage screening strategy for nontargeted lipid analysis, utilizing multiplexed electrophoretic separations with an Orbitrap mass analyzer in negative ion mode. The method successfully identifies and annotates 270 serum lipid features based on accurate mass and relative migration time, offering a powerful tool for lipid research.

TMIC has two main untargeted lipidomics assays:

  • Global (Untargeted) Lipidomics Profiling. Using a cutting-edge method to analyze the lipidome in both positive and negative ionization. It typically detects, identifies and relatively quantifies more than 5,000 lipids for positive ionization and more than 2,000 lipids for negative ionization. This is a one-stop analysis where it includes all sample preparation, lipid extraction, LC-MS analysis, data analysis, lipid identification, data normalization, and statistical analysis (PCA, PLS-DA, Volcano plots)
  • High Throughput Global Metabolomics by MSI-CE-MS for Large-scale Epidemiological and Clinical Studies. This platform employs multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) with multiplexed separations to analyze ionic metabolites from bio-banked samples. This technique accommodates multiple sample types without complex preparation, and it offers up to four MSI-CE-MS configurations. These configurations expand coverage to include polar/ionic metabolites, as well as non-polar/intact lipids, encompassing nonesterified fatty acids and a diverse range of drug metabolites.

Lipidomics and Extracellular Vesicles (EVs)

Lipidomics analysis and EVs are intricately connected due to the vital role that lipids play in the formation, composition, and function of these vesicles. lipidomics analysis provides a comprehensive understanding of the lipid content within extracellular vesicles, influencing their biogenesis, cargo sorting, uptake by recipient cells, and functional roles in intercellular communication. This interplay between lipidomics and extracellular vesicles is essential for unraveling the complexities of cellular communication, disease mechanisms, and potential therapeutic applications. The term “extracellular vesicles” (EVs) is relatively new in the field of science. If you are not familiar with this term, check out the Extracellular Vesicles 101

The 8th Lipidomics Forum of iLS

A Conference of the International Lipidomics Society and Partners. You will get a chance to learn about the latest lipidomics research from your presentations, posters, and of course from the keynote speakers Frances Platt, Giovanni D’Angelo, Maria Fedorova, Valerie O’Donnell, Peter Meikle, Christoph Thiele, Zoltan Takats, Julijana Ivanisevic, and Andrej Shevchenko. This year is located in Vienna, Austria from August 27-30.

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