Dysfunctional B cells found to contribute to age-related metabolic disease

A group of researchers has revealed why fat surrounding organs increases during ageing, providing a drug target for metabolic-related conditions such as diabetes. The study was conducted at Yale University, US.

Previous findings have shown that age reduces the body’s ability to burn fat, consequently leading to increased internal fat around elderly patients’ organs.

The current study demonstrated that the macrophage immune cells required to burn this fat remain active, but the overall numbers declined as fat increased with ageing.

Another finding from the investigation showed that adipose B cells in fat proliferate as animals age, contributing to increased inflammation and metabolic decline. According to the researchers, these adipose B cells are a unique source of inflammation; normally B cells produce antibodies but with ageing become dysfunctional.

When working correctly, some B cells expand as needed to protect the body from infection, then contract to baseline. However, the aged cells do not contract.

“This predisposes an animal to diabetes and metabolic dysfunction like inability to burn fat,” said Dr Vishwa Deep Dixit, the lead researcher of the study. He theorised that this ongoing expansion may be due to increased human life expectancy, which pushes the body’s cells beyond their evolutionary limits. “Several mechanisms in the body are not selected for longevity,” he continued.

Using mice models, adipose B cells were found to expand by receiving signals from nearby macrophages. They also discovered that reducing macrophage signal and removing adipose B cells reversed the expansion process, which protected against age-induced decline in metabolic health.

A suggestion made by the researchers is to repurpose drugs to target these dysfunctional adipose B cells, such as cytokine IL-1B, which reduces one of the small proteins driving this process. Other immunotherapy drugs which neutralise B cells could also be a therapeutic option, say the team.

The results were published in Cell Metabolism.