Sequencing the human genome revolutionized medicine, but scientists quickly realized that genetic blueprints alone could not reveal the body's activities. This requires understanding the proteome—all the proteins expressed by our genes that make up the cellular machinery that performs most of the body's functions. Now, another group of molecules called liposomes -- all the lipids in our bodies -- are filling in more details of human physiology.
Human liposomes, which include all lipids in the human body, are of increasing interest due to their role in human physiology, especially direct influence by diet and intestinal microbes, and their potential in disease intervention, especially in diseases such as type 2 diabetes. A recent study took an in-depth look at liposomes, revealing their relationship to health markers such as insulin resistance, aging, and response to infection, as well as their potential to predict biological aging and guide health interventions.
Lipids are a large class of fat or oily small molecules, including triglycerides, cholesterol, hormones and some vitamins. In our bodies, they form cell membranes, serve as cellular messengers, and store energy; they play key roles in responding to infections and regulating metabolism.
Our genome is basically stable. Our proteome, although influenced by health and environment, is largely determined by the coding of genes. In contrast, our liposomes can be altered directly, in part by what we eat and which microbes live in our gut, making liposomes more plastic and perhaps more responsive to interventions. However, the number and variety of lipid molecules (thousands at least) make them difficult to study.
"Lipids are very understudied," said Michael Snyder, Ph.D., W. Ascherman, MD, FACS Professor of Genetics at Stanford University. "They are involved in nearly every process in the body, but because they are so heterogeneous and numerous, we may not know the true role of most lipids."
A new study from Snyder's lab, published September 11 in the journal Nature Metabolism, is one of the first to take an in-depth look at human liposomes and track how they change in health and disease, particularly during the development of type 2 diabetes.
More than 100 participants, including many at high risk for diabetes, were followed for nine years, providing blood samples every three months when healthy and every few days when sick.
Using mass spectrometry, a technique that separates compounds by molecular mass and charge, the researchers cataloged approximately 800 lipids and their relationship to insulin resistance, viral infections, aging, and more.
The researchers found that while each person's liposomes had a unique profile and remained stable over time, certain types of lipids changed predictably as a person's health progressed.
For example, more than half of the cataloged lipids are related to insulin resistance -- which results in type 2 diabetes when the body's cells are unable to use insulin to take glucose from the blood. While insulin resistance can be diagnosed by measuring blood sugar, understanding changes in liposomes can help uncover the biological processes at play.
"Every molecule associated with a disease has the opportunity to tell us more about the mechanism and potentially become a target that affects disease progression," said Daniel Hornberg, Ph.D., a former postdoc in Snyder's lab and co-first author of the study.
The researchers also identified more than 200 lipids that fluctuate during respiratory viral infections. The rise and fall in these lipid levels matches the body's higher energy metabolism and inflammatory response in the early stages of infection and may indicate the trajectory of the disease. People with insulin resistance have some abnormalities in these responses to infection and a weaker response to vaccination.
The participants ranged in age, from 20 to 79, and the study period was long, allowing the researchers to observe how liposomes change with aging. They found that most lipids, such as cholesterol, increase with age, but a few, including omega-3 fatty acids, decrease with age. Furthermore, these signs of aging with liposomes do not appear at the same rate in everyone. For example, insulin resistance appears to accelerate the onset of these signs.
"This raises an interesting question: whether lipid profiles can predict whether a person's biological aging is faster or slower," said SiWu, Ph.D., co-first author of the study and another former postdoc in Snyder's lab.
Another surprising finding, Wu said, was that certain lipids, such as ether-linked phosphatidylethanolamine, which is considered an antioxidant and is involved in cell signaling, were closely linked to improved health. They could be candidates for new ways of monitoring health, or even as dietary supplements.
Next, Snyder's lab hopes to build on clues from this broad survey to study correlations between specific lipids and lifestyle changes.