Lipidomics, the comprehensive analysis of a cell or organism’s lipid profile, is a subgroup within the field of metabolomics that is rapidly developing into a discipline of its own.
Until recently, a common misconception was that lipids are simply fat molecules, however, recent advances in technologies used to dissect and study lipid profiles prove that this is not the whole truth.
What are lipids, and why study them?
Lipids are complex polymer biomolecules that contain hydrocarbons and are strictly hydrophobic, meaning they do not interact with or dissolve in water. They are key players in metabolic regulation – acting at the cellular level through to an entire organism’s energy control and signaling pathways. Examples of lipids include oils, fats, fat-soluble vitamins, hormones, lipoproteins and lipid droplets.1
“Lipidomics is end point research. If you compare it to, for example, genomics, which is interested in the genes that are almost fixed from birth, lipids on the other hand are a variant of metabolism or part of the metabolism. They change rather continuously as they are influenced by various states, not just because of the lipids you consume as part of your diet, but through disease also,” says Dr. Christian Klose, Head of Research and Development at Lipotype GmbH.
Changes in lipid structure, function and expression can induce diseases such as metabolic disorders, cancer and cardiovascular disease; this is not new knowledge. However, the advanced tools to study and obtain in depth analysis of lipids at the molecular level simply have not been available. Now, by studying the expression and localization of the entire lipid profile, lipidomics, as part of the multidisciplinary “omics” research field, offers a thorough understanding of the pathways through which lipids function as part of a biological system. There is now the potential to identify previously unknown disease biomarkers, improve the diagnosis of lipid-related disease, and develop novel pharmacological therapeutics, further opening the door to personalized medicine.
How do we study the lipidome?
Lipid molecules are complex and diverse in structure, meaning their quantification and identification is no easy task for scientists. Several techniques spanning the fields of analytical chemistry, genomics and bioinformatics are often utilized in parallel to provide whole spectrum lipidome analysis. Commonly adopted methods include spectroscopy, mass spectrometry (MS) and chromatography, however the precise cocktail of techniques used is dependent on whether a researcher wishes to conduct:
- Global lipid analysis profiling, or
- Targeted lipidome analysis
One approach is to extract lipids from a sample and separate them prior to MS analysis using chromatography techniques, such as thin layer chromatography (TLC), gas chromatography (GC) or high-performance liquid chromatography (HPLC). Chromatography coupled with MS enables the detection and separation of lipids that are structurally similar and in the same class. However, huge diversity exists across lipid species’ and their expression levels across cells. Consequently, several time-consuming runs are required to achieve large scale lipid analysis using this method alone.2
“Shotgun” lipidomics allows for high-throughput untargeted lipid analysis. Here, a sample is ionized prior to MS lipid detection. Historically, electrospray ionization (EIS) MS has triumphed above other ionization methods and has achieved much success in lipidomics, consequently making it the most commonly adopted ionization technique in the field.3 A key issue with “shotgun” lipidomics is that it struggles to detect the large number of lipid species estimated to exist (approximately 10-100,000) . Consequently, chromatography-based lipidomics and “shotgun” lipidomics are often used together to complement one another, subject to whether a researcher requires targeted or untargeted lipid analysis.4
Applications of lipidomics: from medicine to make-up
Lipidomics holds the potential to reshape our current approaches to diagnosing medical conditions and provides novel research avenues for therapeutic development. In a recent study,5researchers used MS-based shotgun lipidomics to define the fingerprints of lipid molecular species in cardiovascular disease (CVD). “In clinical assessments, a patient receives a lipid panel, where the doctors basically measure two different types of cholesterol, the “bad” and “good” cholesterol, also known as low-density lipoproteins and high-density lipoprotein, and the total plasma triglyceride levels,” says Klose. “Researchers from Finland analyzed the lipid measurements from the lipid panel vs our lipidomic analysis at the molecular level from several thousand people to see whether they provide the same degree of information on cardiovascular risk prediction. The molecular lipidomic data trumped the panel data by several orders of magnitude and produced detailed coverage of lipid molecular patterns in more than just cardiovascular diseases that previously were not known.”
Neurodegenerative disorder research is an area in which uncertainty surrounding the etiology of certain diseases has halted progress in developing treatments, despite intense research efforts from a protein and gene-centric perspective. This field is also seeing an increasing number of scientists adopting lipidomics analysis. “A very interesting new emerging field is neurolipidomics. Here, researchers focus on neurodegenerative diseases like Alzheimer’s or Parkinson’s because the obvious principle is that your brain is over 50% lipids, so if there is something going wrong with the lipids in your brain, it is likely to impact your lipid metabolism.” says Klose. Particularly, a multi-omics approach may offer novel diagnostic biomarkers for disease detection in the early stages of age-related neurodegenerative diseases.
From medicine to make up, lipidomics can also aid product assessments in the cosmetic and beauty industry. “Surprisingly, the cosmetics and dermatology industry are exploring lipidomics research in relation to their products. Previously, these companies have wanted to claim their products do improve your skin, however, they did not have the methodology to actually prove this. So, they had to rely on studies in which they asked the general population whether they would recommend the product. Of course, this isn’t really scientific evidence, and so they are very interested in harnessing lipidomics and are exploring the field on their own” adds Klose.