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Unraveling the Role of Lipidome in Human Physiology

Lipidome in Human Physiology


The sequencing of the human genome promised a healthcare revolution, yet scientists soon realized that genes alone cannot paint the full picture of the human body’s intricate functions. Enter the proteome – the collection of proteins expressed by our genes, orchestrating the majority of bodily processes. Now, another set of molecules known as the lipidome, encompassing all the lipids within us, is shedding light on the finer nuances of human physiology.

Understanding Lipids:

Lipids constitute a diverse group of small, fatty, or oily molecules, encompassing triglycerides, cholesterol, hormones, and certain vitamins. Within our bodies, they form cell membranes, act as messengers between cells, store energy, respond to infections, and regulate metabolism.

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Dynamic Nature of the Lipidome:

While our genome remains relatively stable and the proteome relies heavily on genetic encoding, the lipidome is remarkably flexible. It can be directly influenced by dietary choices and the microbial inhabitants of our gut, rendering it adaptable and potentially receptive to interventions. However, due to the sheer number and diversity of lipid molecules – numbering in the thousands – studying them has proven challenging.

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The Understudied Lipids:

Despite their involvement in a multitude of biological processes, lipids have remained understudied. As Dr. Michael Snyder, the Stanford W. Ascherman, MD, FACS Professor in Genetics, points out, “They are involved in pretty much everything, but because they’re so heterogeneous, and there are so many of them, we probably don’t know what most lipids really do.”

A New Frontier: Research into the Human Lipidome:

A groundbreaking study from Dr. Snyder’s laboratory, published in Nature Metabolism on September 11th, delves deeply into the human lipidome. It examines how the lipidome evolves under both healthy and diseased conditions, with a particular focus on Type 2 diabetes development.

Indicators of Health:

Over 100 participants, including individuals at risk of diabetes, were monitored for up to nine years. Blood samples were collected regularly, providing insights into lipid changes during health and illness. Using mass spectrometry, a technique separating compounds by their molecular properties, researchers cataloged approximately 800 lipids and their correlations with insulin resistance, viral infections, aging, and more.

Key Findings:

The study revealed that while each person’s lipidome carries a unique signature that remains consistent, specific lipid types change predictably with an individual’s health status. For instance, more than half of cataloged lipids were associated with insulin resistance, a precursor to Type 2 diabetes. Understanding lipidome changes can unveil the underlying biological processes.

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Insights into Infection and Aging:

The research also identified over 200 lipids that fluctuate during respiratory viral infections. These lipid fluctuations mirror heightened energy metabolism and early infection inflammation, offering potential insights into disease trajectories. Notably, those with insulin resistance exhibited variations in their response to infection and a weakened reaction to vaccinations.

Aging and Lipidome:

With participants spanning ages 20 to 79 years, the study illuminated how the lipidome transforms with age. While most lipids, including cholesterol, increase with aging, certain ones, like omega-3 fatty acids known for their health benefits, decrease. Remarkably, these aging indicators do not progress at the same pace in all individuals, with insulin resistance seemingly accelerating the process.

Promising Health Indicators:

Surprisingly, certain lipid groups, such as ether-linked phosphatidylethanolamines believed to be antioxidants and involved in cell signaling, consistently correlated with better health. These may emerge as candidates for novel health monitoring methods or even dietary supplements.

Future Investigations:

Dr. Snyder’s lab aims to follow up on these insights, exploring correlations between specific lipids and lifestyle choices, paving the way for a deeper understanding of the role of the lipidome in human health.