Scientists have discovered a surprising reason why excess belly fat can lead to type 2 diabetes — and a potential new way to stop it.
Researchers at the University of Pittsburgh School of Medicine found that a special group of “good” immune cells inside fat tissue plays a crucial role in keeping blood sugar under control.
Their findings, published in Nature Communications, could lead to new treatments that prevent or even reverse insulin resistance, the main driver of type 2 diabetes.
For years, doctors have known that visceral fat — the fat stored deep in the abdomen around organs — increases the risk of diabetes.
This type of fat releases inflammatory signals that interfere with the body’s ability to use insulin, the hormone that regulates blood sugar. When insulin stops working properly, blood sugar levels rise and diabetes develops.
The new research reveals that not all immune activity in fat is harmful. The team discovered a group of protective immune cells, known as resident macrophages, that actually reduce inflammation and help keep fat tissue healthy.
These cells clean up damaged tissue and prevent harmful immune reactions. As long as they are present, they help the body respond normally to insulin.
However, when a person gains too much visceral fat, inflammation increases and a key protein called SerpinB2 drops sharply. This protein is essential for the survival of resident macrophages. Without it, the helpful cells die off, allowing inflammation to spiral out of control. Fat tissue then grows larger and more inflamed, which worsens insulin resistance and raises the risk of diabetes.
To test whether this process could be reversed, the researchers conducted experiments in overweight mice with insulin resistance. When the animals were given antioxidant supplements, the number of protective immune cells increased and their ability to respond to insulin improved. This suggests that restoring the balance of immune cells in fat tissue could be a powerful strategy for treating metabolic disease.
The research team is now working to translate these findings into treatments for people. Their goal is to develop a medication that boosts SerpinB2 levels, helping the beneficial immune cells survive and function properly. Such a drug could prevent harmful fat buildup and inflammation, potentially stopping diabetes before it begins or improving the condition in those who already have it.
The discovery could also complement existing weight-loss medications known as GLP-1 drugs. While these treatments can be effective, some patients eventually stop responding to them. Researchers believe that protecting the healthy immune cells in fat tissue might enhance or extend the benefits of these therapies.
With obesity rates rising worldwide, scientists say understanding how fat tissue affects the immune system is critical for tackling chronic diseases. This study highlights that fat is not just a storage site for energy but an active organ that influences health in complex ways.
By targeting the immune system inside fat, future treatments may be able to address the root causes of insulin resistance rather than just managing symptoms. The findings offer new hope that type 2 diabetes could one day be prevented or even reversed through innovative therapies.
