Stanford Scientists Uncover New Indicators of Health, Disease, and … – SciTechDaily

The human lipidome, encompassing all the bodys lipids, is gaining attention for its role in human physiology, particularly its direct influence by diet and gut microbes, and its potential in disease intervention, especially in conditions like Type 2 diabetes. A recent study dives deep into the lipidome, revealing its association with health indicators like insulin resistance, aging, and response to infections, and its potential for predicting biological aging and guiding health interventions.

The sequencing of the human genome promised a revolution in medicine, but scientists soon realized that a genetic blueprint alone does not show the body in action. That required understanding the proteome all the proteins, expressed by our genes, forming the cellular machinery that performs the bulk of the bodys functions. Now, another set of molecules known as the lipidome all the lipids in our bodies is filling in more details of human physiology.

Lipids are a broad category of small, fatty, or oily molecules, including triglycerides, cholesterol, hormones, and some vitamins. In our bodies, they make up cell membranes, act as cellular messengers, and store energy; they play key roles in responding to infection and regulating our metabolism.

Our genome is essentially stable. Our proteome, though influenced by our health and environment, is largely dependent on whats encoded by our genes. In contrast, our lipidome can be directly altered, in part, by what we eat and which microbes live inside our gut, making it more malleable and perhaps more responsive to interventions. But the number and variety of lipid molecules there are at least thousands has made them hard to study.

Lipids are very understudied, saidMichael Snyder, PhD, the Stanford W. Ascherman, MD, FACS Professor in Genetics. They are involved in pretty much everything, but because theyre so heterogeneous, and there are so many of them, we probably dont know what most lipids really do.

A new study from Snyders lab, published Sept.11inNature Metabolism, is among the first to deeply dive into the human lipidome and track how it changes under healthy and diseased conditions, particularly in the development of Type 2 diabetes.

More than 100 participants, including many at risk for diabetes, were tracked for up to 9 years, providing blood samples every three months when healthy and every few days during illness.

Using mass spectrometry techniques, which separate compounds by their molecular mass and electric charge, researchers cataloged some 800 lipids and their associations with insulin resistance, viral infection, aging, and more.

The researchers found that although everyones lipidome has a distinctive signature that remains stable over time, certain types of lipids changed predictably with a persons health.

For example, more than half of the cataloged lipids were associated with insulin resistance when the bodys cells cannot use insulin to take up glucose from the blood which can lead to Type 2 diabetes. Though insulin resistance can be diagnosed by measuring blood glucose, understanding changes to the lipidome helps uncover the biological processes at work.

Every molecule that is associated with a disease has a chance of telling us more about the mechanism and may be serving as a target for affecting the disease progression, said Daniel Hornburg, Ph.D., a former post-doctoral scholar in Snyders lab and co-lead author of the study.

The researchers also identified more than 200 lipids that fluctuate over the course of a respiratory viral infection. Rising and falling levels of these lipids matched the bodys higher energy metabolism and inflammation in early infection, and may indicate the trajectory of the disease. Those with insulin resistance showed some anomalies in these responses to infection as well as a weaker response to vaccinations.

The wide age range of the participants 20 to 79 years old and the length of the study allowed the researchers to see how the lipidome changes with aging. They found that most lipids, such as cholesterol, increase with aging, but a few, including omega-3 fatty acids, known for their health benefits, decrease. Moreover, these signs of aging in the lipidome do not occur at the same rate in everyone. Insulin resistance, for example, seems to accelerate them.

It raises the interesting question of whether lipid profiles could predict whether an individual is biologically aging more quickly or more slowly, said Si Wu, PhD, co-lead author of the studyand another former postdoc in Snyders lab.

Another surprising insight, Wu said, was how consistently certain groups of lipids, such as ether-linked phosphatidylethanolamines, which are thought to be antioxidants and involved in cell signaling, were associated with better health. They may be candidates for new ways to monitor health or even taken as dietary supplements.

Next, Snyders lab hopes to follow leads from this broad survey to look at correlations between specific lipids and lifestyle changes.

Reference: Dynamic lipidome alterations associated with human health, disease and ageing by Daniel Hornburg, Si Wu, Mahdi Moqri, Xin Zhou, Kevin Contrepois, Nasim Bararpour, Gavin M. Traber, Baolong Su, Ahmed A. Metwally, Monica Avina, Wenyu Zhou, Jessalyn M. Ubellacker, Tejaswini Mishra, Sophia Miryam Schssler-Fiorenza Rose, Paula B. Kavathas, Kevin J. Williams and Michael P. Snyder, 11 September 2023,Nature Metabolism. DOI: 10.1038/s42255-023-00880-1

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