Obesity and type 2 diabetes affect hundreds of millions of people around the world. These conditions are known for causing problems with blood sugar and body weight, but their effects reach far beyond that.
People with obesity and type 2 diabetes also have a much higher risk of developing heart disease, strokes, and other serious problems involving the blood vessels.
One reason for this increased risk is that obesity and diabetes can damage the lining of blood vessels. Healthy blood vessels are flexible and can widen or narrow as needed to control blood flow.
However, in people with metabolic diseases, blood vessels often become inflamed and stiff. Over time, this damage can increase the chances of heart attacks, strokes, and poor circulation.
A new study led by researchers at the University of Zurich has uncovered an unexpected way to improve blood vessel health. The researchers discovered that changing molecular signals in a thin layer of fat that surrounds blood vessels could reduce inflammation and restore healthier vessel function. The findings were published in the journal Cell Reports.
Most people think of body fat simply as stored energy. However, scientists now know that fat is also an active tissue that constantly communicates with other organs.
The thin layer of fat surrounding arteries and veins is called perivascular fat. In healthy people, this fat helps blood vessels function properly by sending chemical signals that support normal blood flow and keep inflammation under control.
The situation changes in obesity and type 2 diabetes. The perivascular fat becomes inflamed and starts behaving differently. The fat cells store lipids in abnormal ways and release substances that make blood vessels stiffer and less responsive. As this process continues, the risk of vascular disease steadily rises.
The researchers wanted to understand why these harmful changes occur. Instead of focusing on individual genes, they examined epigenetics.
Epigenetics refers to chemical signals that determine how genes are used without changing the DNA itself. Every cell contains the same genes, but epigenetic signals help decide which genes are switched on and which remain inactive.
These signals act like instructions that tell cells how to behave. In perivascular fat, changes in these instructions can turn on genes that promote inflammation and damage blood vessels.
The research team from the University of Zurich, University Hospital Zurich, and the University of Pisa tested special medicines known as BET protein inhibitors in both mice and human tissue samples. These medicines target proteins that read epigenetic signals and influence the activity of many genes at once.
The scientists found that the drugs changed the behavior of perivascular fat. The fat became less inflammatory and released fewer harmful substances. Blood vessels surrounded by this reprogrammed fat relaxed more easily and showed fewer signs of damage.
The researchers also identified an important enzyme called hexokinase 2. This enzyme helps cells process sugar. When it becomes overactive in perivascular fat, it causes fat cells to store more fat and release more inflammatory molecules that damage blood vessels. Reducing the activity of this enzyme helped calm inflammation and improve blood vessel function.
Professor Francesco Paneni, who led the study, explained that the goal was to reset the entire program controlling gene activity in the fat tissue rather than targeting one harmful molecule at a time.
The findings suggest a possible new direction for medicine. Current treatments often focus on problems that appear after damage has already started, such as high blood pressure, high cholesterol, or elevated blood sugar. The new approach aims to intervene much earlier by reprogramming the tissue processes that contribute to vascular damage.
Study analysis: This study provides exciting evidence that blood vessel damage associated with obesity and type 2 diabetes may not be irreversible. By changing the epigenetic instructions that control fat surrounding blood vessels, researchers were able to reduce inflammation and improve vascular function in both animal and human tissues.
However, the work was conducted mainly in laboratory settings, and it remains unknown whether these treatments will prove safe and effective in patients. Larger clinical studies will be needed before these approaches can become routine treatments.
Nevertheless, the findings open the possibility of preventing heart attacks and strokes by addressing the underlying biological processes much earlier than current therapies.
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Source: University of Zurich.
