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Understanding Oxysterols—These Bioactive Lipids are the Essential New Tool in Metabolomic, Immune, and Inflammation Research

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There are four categories of sterols: synthetic sterols, mycosterols (of fungal origin), zoosterols (of animal origin), and phytosterols (of plant origin).1 Phytosterols in particular—from sitosterol to campasterol—lower blood low-density lipoproteins (LDL) levels. However, when sterols are oxidized, toxic oxysterols can be created.1

These oxysterols are bioactive lipids. Recent research documented their direct correlation with atherosclerotic lesions (plaques).1 Certain oxysterols advance atherosclerosis even more so than cholesterol, so a thorough understanding of oxysterols as they relate to metabolism and oxidation of sterols is essential.2,3,4

Oxysterols Contribute to Inflammation and Immune Responses

Oxysterols contribute to inflammation due to expression and synthesis of inflammatory cytokines, adhesion molecules, and chemokines.1 This expression is attributed to the activity of nuclear factor κB (NF-κB). NF-κB is a transcription protein that is regulated by cholesterol oxidation products which activate the expression of protein kinase C, leading to the expression of NF-κB.1

Further, with inflammation noted as a leading cause of complications for an array of chronic diseases, oxysterols’ contribution to inflammation makes them a key component in comprehensively understanding various diseases and treatments. In addition, phagocyte activation, a trait of inflammations, drives nonradical and radical reactive oxygen species alike, making for an even greater inflammation response.

In addition to the connection with inflammation, studies demonstrate that oxysterols have a central role in mediating various diseases, from age-related degenerative disorders to cancer.5,6

Oxysterols Can be Used to Predict Future Complications

Beyond their connection to driving inflammation, the presence of oxysterols may predict the pathogenesis of future diseases. The presence of oxysterols has been linked to several diseases, most notably atherosclerosis.1 Additionally, research has revealed correlations between oxysterols and a variety of malignancies, including Alzheimer’s disease, breast cancer, diabetes mellitus, infertility, lung cancer, multiple sclerosis, and osteoporosis.6

Using targeted metabolomics to better understand the relationship of oxysterols to oncology and degenerative disease states may lead to advances in therapeutic research and predictive screening, but more research is required to make any significant claims.

The Future for Routine Metabolomic Analyses of Oxysterols

The possibilities of oxysterols in research are vast, as they may be used for the prediction and early detection of diseases, drug development, and disease recovery. For example, oxysterols have been linked to neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.7

With Metabolon’s growing global metabolomic library and validated panels we’re excited to contribute to your oxysterols research, helping you gain insights more quickly and ultimately get closer to understanding and combating many major diseases. Routine oxysterol analysis is a fast-growing field of exploratory research, and we’ll continue to share our insights along with new research as discoveries are uncovered.

Ready to see what new insights oxysterols can help your research reveal?
Contact us today to discuss your project or study.

References

1. Brzeska, M., Szymczyk, K., Szterk, A. Current Knowledge about Oxysterols: A Review. Journal of food science. 2016; 81: 2299-2308. DOI: https://doi.org/10.1111/1750-3841.13423

2. Jacobson MS, Price MG, Shamoo AE, Heald FP. Atherogenesis in White Carneau pigeons effects of low-level cholestane-triol feeding. Atherosclerosis. 1985; 57(2–3): 209–17.

3. Staprans I, Pan XM, Rapp JH, Feingold KR. Oxidized cholesterol in the diet is a source of oxidized lipoproteins in human serum staprans. J Lipid Res. 2003; 44(4): 705–15.

4. Meynier A, Lherminier J, Demaison-Meloche J, Ginies C, Grandgirard A, Demaison L. Effects of dietary oxysterols on coronary arteries in hyperlipidaemic hamsters. Br J Nutr. 2002; 87(5): 447–58.

5. Poli G, Biasi F, Leonarduzzi G. Oxysterols in the pathogenesis of major chronic diseases. Redox Biol. 2013; 1(1): 125–30.

6. Samadi, A., et al. A comprehensive review on oxysterols and related diseases. Curr Med Chem. 2021; 28(1): 110-136. doi: 10.2174/0929867327666200316142659

7. Griffiths, W.J., Wang, Y. Oxysterol research: a brief review. Biochem Soc Trans. 2019; 47(2): 517–526. 

Deirdre Hauser
Deirdre Hauser is the manager of the Clinical and Targeted Analysis Method Development Team, and the technical supervisor of Metabolon's CAP/CLIA compliant quantitative diagnostic testing laboratory. She has over 20 years of LC-MS/MS method development and validation experience with both endogenous and exogenous analytes.

Topics

Cardiovascular | Inflammation | Neurology | Oncology

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