A matter of fat: lipidomics applications in health and disease

As a branch of metabolomics, lipidomics is aimed at full analysis of lipid species and their biological roles with respect to health and diseases. In the last 10 years, it has attracted increasing attention as a research tool in a wide range of disciplines including physiology, lipid biochemistry, clinical biomarker discovery and pathology. Unless lipids were considered in the past to be only membrane components or an energy store, today we know they play critical roles in cell signaling transduction processes. [1,2] Furthermore, lipid metabolism is found to be critically aberrant in several different human diseases such as diabetes, obesity, atherosclerosis and Alzheimer’s disease. [3–6] All these characteristics make lipids profiling an essential tool not only for investigation of many pathological processes but also in identifying potential biomarkers for establishing preventive or therapeutic approaches for human health. Unlike other biomolecules, lipids do not possess a certain individual structure, making lipidomics analysis an analytical challenge in which mass spectrometry (MS) represents a powerful approach. Here we present a direct infusion MS approach (shotgun lipidomics) in order to detect (and quantify) at least 10 lipid species from human blood using a two-step extraction procedure, in order to detect also polar metabolites. Moreover, we developed a data analysis pipeline, which allows for the fast and robust quantification and identification of lipid species from high-resolution MS data. Isotope-corrected and calibrated mass traces are matched to an in-house database combining data from LipidMaps and HMDB. Internal standards serve as control for mass calibration as well as for abundance normalization for their respective lipid class. As proof of principle, we combined our approach to a simple, fast, and minimally invasive blood sampling method. Starting from 20 µL human capillary blood from 15 volunteers, around 300 lipid species covering all main lipid classes were identified (and semi-quantify) by direct infusion-MS. This shotgun MS approach was also applied to different type of biological samples such as cells, different human tissues (liver, muscle, and white adipose tissues) and stratum corneum. This in order to study the effects of lifestyle factors (such as diet) and/or biological active compounds on lipid profile.