In a Recent Study, Researchers Reveal the Pivotal Role of Lipids in Aging, Health, and Disease
In a recent study published in the journal Nature Metabolism, a team of researchers conducted detailed longitudinal profiling and analysis of the lipidome using plasma samples from over a hundred participants over nine years to understand the roles of various types of lipids in health, aging, and disease in humans.
Background
Lipids play essential roles in the human body in processes such as cell signaling, maintenance of cellular structure, and energetics. They can have exogenous or endogenous origins and come in various forms and sizes, with subclasses comprising:
- Triacylglycerols
- Phosphatidylethanolamines
- Cholesterol esters
- Lysophosphatidylcholines
- Ceramides
- Lysophosphatidylethanolamines
However, despite the critical roles that lipids play in the human body, there is a paucity of information on the change in lipids in individuals over time and in relation to diseases.
About the Study
In the present study, the researchers characterized the lipid profiles of over 100 participants over a period of nine years, using a mass spectrometry approach to rigorously, quantitatively, and rapidly measure a wide array of lipids. Plasma samples were used for the lipid profiling and collected at ten different time points across the nine years from the participant group, which comprised of individuals with insulin resistance and sensitivity.
Plasma samples were collected every three months when the participants were healthy and three to seven times across three weeks when a participant was unwell. Apart from the lipid profile, other clinical laboratory parameters were also measured for each sample. Furthermore, 62 chemokines, cytokines, and growth factors were also profiled for each sample since the samples were obtained during periods of illness or stress.
A quantitative, high-throughput lipidomic pipeline comprising a triple-quadrupole mass spectrometer was used to carry out the lipid profiling, along with a device to perform differential mobility separation. This method can perform quantification and identification of over a thousand lipids belonging to 16 subclasses, including lysophosphatidylcholines, free fatty acids, triacylglycerides, diacylglycerols, and various types of ceramides, among others.
Results
The findings indicated that aging, insulin resistance, and viral infections of the respiratory system were associated with dynamic changes in the lipidome. These observations suggested that lipids play a significant role in inflammation regulation and homeostasis of the immune system. Additionally, immune homeostasis was found to be disturbed in individuals with insulin resistance, with the association between clinical markers and lipids also showing alterations and various lipid subclasses showing accelerated changes during aging.
The researchers found that lipid subclasses play specific biological functions, and the conventional lipid profiles that are measured clinically often lack the resolution required for understanding metabolic health. The results also showed that ester-linked phosphatidylethanolamines, which are also antioxidants known to be involved in cell-signaling, were correlated with healthy phenotypes with high high-density lipoprotein levels and low steady-state plasma glucose.
Furthermore, the levels of ester-linked phosphatidylethanolamines were found to decrease in the early stages of infection, resulting in an increase in inflammation, and phosphatidylethanolamines also showed insulin resistance or insulin sensitivity and sex-related signatures with aging.
Conclusions
Overall, this comprehensive longitudinal analysis of the lipidome using a large sample set revealed that lipids play a critical role in health and disease and can serve as important biomarkers and targets for preventative and therapeutic strategies. Furthermore, specific lipid subclasses also showed age and sex-specific signatures, indicating a need for differential therapeutic approaches.
Journal reference: Hornburg, D., Wu, S., Moqri, M., Zhou, X., Contrepois, K., Bararpour, N., Traber, G. M., Su, B., Metwally, A. A., Avina, M., Zhou, W., Ubellacker, Jessalyn M, Mishra, T., Sophia, R., Kavathas, P. B., Williams, K. J., & Snyder, M. P. (2023). Dynamic lipidome alterations associated with human health, disease and ageing. Nature Metabolism.
