In a recent study published within the journal Nature Metabolism, a team of researchers conducted detailed longitudinal profiling and evaluation of the lipidome using plasma samples from over 100 participants over nine years to grasp the roles of varied forms of lipids in health, aging, and disease in humans.

Study: Dynamic lipidome alterations related to human health, disease and ageing. Image Credit: Vladimir Sukhachev / Shutterstock

Background

Lipids play essential roles within the human body in processes equivalent to cell signaling, maintenance of cellular structure, and energetics. They will have exogenous or endogenous origins and are available various forms and sizes, with subclasses comprising triacylglycerols, phosphatidylethanolamines, cholesterol esters, lysophosphatidylcholines, ceramides, and lysophosphatidylethanolamines. Nevertheless, despite the critical roles that lipids play within the human body, there may be a paucity of knowledge on the change in lipids in individuals over time and in relation to diseases.

The event of recent technologies in high-throughput omics has made it possible to check human physiology and the changes that occur within the molecular landscape during disease. Nevertheless, while next-generation sequencing and latest strategies in mass spectrometry have made the study of genomics and proteomics more accessible and cost-effective, the complex diversity of metabolites within the body has been a challenge within the understanding of metabolomics. Lipids constitute a significant a part of the metabolome and play a big role in mediating inflammatory processes, which makes understanding longitudinal lipidome changes essential for understanding disease pathophysiologies.

In regards to the study

In the current study, the researchers characterised the lipid profiles of over 100 participants over a period of nine years, using a mass spectrometry approach to carefully, quantitatively, and rapidly measure a big selection of lipids. Plasma samples were used for the lipid profiling and picked up at ten different time points across the nine years from the participant group, which comprised 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. Other than the lipid profile, other clinical laboratory parameters were also measured for every sample. Moreover, 62 chemokines, cytokines, and growth aspects were also profiled for every sample for the reason that samples were obtained during times of illness or stress.

A quantitative, high-throughput lipidomic pipeline comprising a triple-quadrupole mass spectrometer was used to perform the lipid profiling, together with a tool 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 forms of ceramides, amongst others.

The baseline lipidome was first characterised using 802 healthy samples obtained from 96 participants who reported no acute disease on the onset of the study. Moreover, those lipid subclasses that showed the very best degree of difference between individuals were also observed to grasp to what degree the variation could possibly be attributed to differences between participants. The association between the worldwide lipidome profile derived from the healthy baseline measurements and the opposite clinical measures was also examined, and for those lipids that showed a negative correlation to clinical measures, the researchers also examined the association between the lipid and the microbiome.

Results

The findings indicated that aging, insulin resistance, and viral infections of the respiratory system were related to dynamic changes within the lipidome. These observations suggested that lipids play a big role in inflammation regulation and homeostasis of the immune system. Moreover, 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 standard lipid profiles which might be measured clinically often lack the resolution required for understanding metabolic health. The outcomes also showed that ester-linked phosphatidylethanolamines, that 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.

Moreover, the degrees of ester-linked phosphatidylethanolamines were found to diminish within the early stages of infection, leading to a rise in inflammation, and phosphatidylethanolamines also showed insulin resistance or insulin sensitivity and sex-related signatures with aging.

Conclusions

Overall, this comprehensive longitudinal evaluation of the lipidome using a big sample set revealed that lipids play a critical role in health and disease and might function essential biomarkers and targets for preventative and therapeutic strategies. Moreover, specific lipid subclasses also showed age and sex-specific signatures, indicating a necessity for differential therapeutic approaches.