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,5 researchers 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.
Lipotype call for international excellence in lipidomics
Lipotype recently announced their Lipidomics Excellence Award (LEA) for breakthrough Lipidomics Projects. The award aims to recognize innovative research and provide technological support to scientists who believe their results can be boosted by a detailed lipid analysis. “The lipidomics community should not be limited to those who are actively researching lipidomics. LEA encourages researchers to incorporate lipidomic analysis in to their work with the hope being that we foster creative power in life sciences research and allow for general progress across disciplines,” adds Henri Deda, who oversees the award organization. Applications are encouraged from a variety of fields including basic science, clinical, medical and pharmacological research, nutrition, diet and food investigations, in addition to dermatological and cosmetic research.
How will the LEA provide a platform for scientists to progress their research? “We will provide 55,000 EUR worth of comprehensive lipid analysis, in addition to statistical analysis so that we can really dig deep into the data and help interpret the finding.” The winner will also present their project to the European Molecular Biology Organization’s “Lipid function in health and disease” workshop taking place September 2019 in Dresden, Germany. “This can really facilitate the research. The media coverage will draw the public eye to the project, and so the first prize winner will receive significant attention in their field. What’s more is the general public will learn about lipidomics research, increasing its accessibility,” Deda notes.
1. Huang H, Akhtar MZ, Ploeg R, Kessler BM (2014) Lipidomics Techniques and its Applications in Medical Research. J Glycomics Lipidomics 4:115. DOI: 10.4172/2153-0637.1000115.
2. Lydic, T and Goo, Y. (2018). Lipidomics unveils the complexity of the lipidome in metabolic diseases. Clinical and Translational Medicine, 7(1). DOI: 10.1186/s40169-018-0182-9.
3. Yang, K. and Han, X. (2011). Accurate Quantification of Lipid Species by Electrospray Ionization Mass Spectrometry — Meets a Key Challenge in Lipidomics. Metabolites, 1(1), pp.21-40. DOI: 10.3390/metabo1010021.
4. Jurowski, K., Kochan, K., Walczak, J., Barańska, M., Piekoszewski, W. and Buszewski, B. (2017). Analytical Techniques in Lipidomics: State of the Art. Critical Reviews in Analytical Chemistry, 47(5), pp.418-437. DOI: 10.1080/10408347.2017.1310613.
5. Abassum R, Rämö JT, Ripatti P, Koskela JT, Kurki M, Karjalainen J, Hassan S, Nunez-Fontarnau J, Kiiskinen TTJ, Söderlund S, Matikainen N, Gerl MJ, Surma MA, Klose C, Stitziel NO, Laivuori H, Havulinna AS, Service SK, Salomaa V, Pirinen M, Jauhiainen M, Daly MJ, Freimer NB, Palotie A, Taskinen MR, Simons K, Ripatti S. (2018). Genetics of human plasma lipidome: Understanding lipid metabolism and its link to diseases beyond traditional lipids. BioRxiv. DOI: 10.1101/457960.