From the discovery of biomarkers for rare diseases to improving our understanding of the progression of Alzheimer’s disease, lipid research is showing significant potential in the field of bioscience. Thanks to recent advancements in mass spectroscopy (MS), lipid research has ever-growing applications in bioscience.

Lipids: the bare necessities of life

Lipids are vital building blocks of living organisms, essential to cell structure and signaling, and energy metabolism. Lipids are a very large family of non-homogenous compounds that typically consist of two hydrophobic, fatty acid tails, a glycerol backbone and a hydrophilic phosphate head. According to the LIPID Metabolite and Pathway Strategy (LIPID MAPS) project, lipids can be categorised into eight major groups: fatty acyls, glycerophospholipids, glycerolipids, sterol lipids, sphingolipids, polyketides, prenol lipids and saccharolpidpids.1

By virtue of their partially hydrophobic nature, lipids are the physical foundation of all living systems, providing the lipid bilayer cell wall that separates living cells from their environment. Lipids have vital functions in extra- and intracellular signal transduction and in the magnification of cellular regulatory cascades.2 Lipids are major participants in the conversion of energy within cells, the transportation of substances, and cell growth, differentiation and apoptosis. As lipids have such critical biological roles, any deviations from their regular function can result in a variety of diseases.

The dawn of lipid research

Lipid research encompasses the large-scale profiling of cellular lipids, the quantification of specific lipids in biological samples and the documentation of the interactions between lipids and other lipids, proteins and metabolites within the body.3 Serious developments in the field have occurred in recent memory, thanks to significant advances in MS and biobanking. Lipid analysis can be challenging due to the sheer number of different cellular lipids, which can range from tens to hundreds of thousands, and their varied concentration in samples. On top of this, lipids are changing constantly in response to changes in their environment and interactions with metabolites.4

Lipids are highly diverse and dynamic molecules which can make profiling an arduous task. Before the implementation of high-throughput lipodomics, lipid profiling was time-consuming and extremely limited. Technological advances in MS techniques have revolutionised the field, enabling the profiling of thousands of lipids in a single assay. Today, lipid research has started to map the lipidome of human cells and describe lipid biological pathways. The rate at which our understanding of lipid behaviour is changing looks set to revolutionise the way we diagnose and treat many diseases.

How lipid research is shaping the future of bioscience

Oncology

Cancerous cells undergo major changes in lipid metabolism, meaning that lipids play a major role in the proliferation of cancerous tumours.4 Lipid research can monitor these changes to discover novel biomarkers for earlier diagnosis. Also, both quantitative and qualitative analysis of lipids in bodily fluids is proving to be a valuable tool for monitoring treatment efficacy and toxicity.4 For example, eicosanoids have been identified to play a role in cancerous cells’ neoplastic transformations and blocking eicosanoid receptors can impede the inflammatory response of tumour cells.6

Metabolic syndromes

Lipid research plays a pinnacle role in understanding how to treat metabolic-syndrome-related diseases like diabetes. Lipidomic techniques are highly utilised for mechanistic assays, risk prediction, and monitoring treatment efficacy. Recent lipid research has shown that phospholipids are key bioactive constituents of high-density lipoprotein (HDL), providing new evidence in favour of the efficacy of HDL therapies in treating cardiovascular disease.7

Neurological disorders

Lipids are major components of the brain, required for signaling, metabolism, trafficking and homeostasis, making lipid research fundamental to studying neurological disorders. Lipid research has revealed the association between long-chain cholesterol esters and Alzheimer’s disease, providing potential novel therapeutic targets such as cholesteryl esters and HDL-C.8

Precision medicine

The most recent direction of lipid research is towards precision medicine. Lipids make up a large proportion of all metabolites, making them important potential biomarkers. Lipid research is accelerating the discovery of biomarkers and the development of targeted therapies, helping to path the way in more personalised therapies for many diseases, from rare metabolic diseases to atherosclerosis.

The ever-growing applications of lipid research in bioscience looks highly promising for this vital research field. With its ever-expanding applications, lipid research is now helping genomic and proteomic research to path the way to better patient diagnosis, treatment and overall outcomes in bioscience.

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References

  1. Fahy, E., Subramaniam, S., Murphy, R.C., Nishijima, M., Raetz, C.R.H., Shimizu, T., Spener, F., van Meer, G., Wakelam, M.J.O. and Dennis, E.A. (2009). Update of the LIPID MAPS comprehensive classification system for lipids. Journal of lipid research, [online] 50 Suppl(Suppl), pp.S9-14. doi: https://doi.org/10.1194/jlr.R800095-JLR200.
  2. Züllig, T., Trötzmüller, M. and Köfeler, H.C. (2019). Lipidomics from sample preparation to data analysis: a primer. Analytical and Bioanalytical Chemistry, 412(10), pp.2191–2209. doi: https://doi.org/10.1007/s00216-019-02241-y.
  3. Valerie Bridget O'Donnell, Ekroos, K., Gerhard Liebisch and Michael J.O. Wakelam (2019). Lipidomics: Current state of the art in a fast moving field. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 12(1). doi: https://doi.org/10.1002/wsbm.1466.
  4. Yang, K. and Han, X. (2016). Lipidomics: Techniques, Applications, and Outcomes Related to Biomedical Sciences. Trends in Biochemical Sciences, 41(11), pp.954–969. doi: https://doi.org/10.1016/j.tibs.2016.08.010.
  5. Titz, B., Gadaleta, R., Lo Sasso, G., Elamin, A., Ekroos, K., Ivanov, N., Peitsch, M. and Hoeng, J. (2018). Proteomics and Lipidomics in Inflammatory Bowel Disease Research: From Mechanistic Insights to Biomarker Identification. International Journal of Molecular Sciences, [online] 19(9), p.2775. doi: https://doi.org/10.3390/ijms19092775.
  6. Virgili, E., Emili, R., Ferri, H., Palermo, F., Calza, L., M Gardarelli and Spina, M. (2018). Lipidomics and Nutrylipidomics in Oncology: Review of the Literature. Journal of bioinformatics and systems biology, 01(01). doi: https://doi.org/10.26502/jbsb.5107002.
  7. Darabi, M., Guillas-Baudouin, I., Le Goff, W., Chapman, M.J. and Kontush, A. (2016). Therapeutic applications of reconstituted HDL: When structure meets function. Pharmacology & Therapeutics, [online] 157, pp.28–42. doi: https://doi.org/10.1016/j.pharmthera.2015.10.010.
  8. Petroula Proitsi, Kim, M., Whiley, L., Pritchard, M., Leung, R., Hilkka Soininen, Iwona Kłoszewska, Patrizia Mecocci, Tsolaki, M., Vellas, B., Sham, P., Lovestone, S., Powell, J., Dobson, R. and Legido-Quigley, C. (2015). Plasma lipidomics analysis finds long chain cholesteryl esters to be associated with Alzheimer’s disease. Translational Psychiatry, 5(1), pp.e494–e494. doi: https://doi.org/10.1038/tp.2014.127.