Longevity Briefs: Could Obesity Turn A Beneficial Drug Into A Harmful One?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: We know that adipose tissue (fat) sends important signals that influence a range of bodily functions, including the immune system. The immune system maintains a balance between cells and signalling molecules that promote inflammation (a process that helps kill pathogens, but damages healthy tissue in the process) and those cells that regulate and suppress inflammation. Researchers have known for a long time that obesity alters the immune system, shifting the balance of the immune response in favour of inflammation. Because of this, it is possible that some inflammatory diseases might progress differently in obese people when compared with non-obese people.

What did the researchers do: In this study, researchers wanted to study how atopic dermatitis, the most common form of eczema, was affected by obesity in mice. To do this, they used chemicals to trigger atopic dermatitis in the ears of obese and non-obese mice. They then studied how obesity affected the disease at the cellular level, and how they responded to conventional treatments.

Key takeaway(s) from this research: The first finding was that the disease was more severe in obese mice, whose ears swelled more than twice as much as the lean mice. The more surprising finding was at the cellular level: rather than simply being a more severe version of the disease, there were fundamental differences when it came to which cell types were responsible for driving the condition. Specifically, there were differences the types of T helper cells present.

T helper cells are a group of white blood cells that coordinate the immune response by releasing signals that boost or inhibit the activities of other immune cells. Multiple subsets of T helper cells exist. In the lean mice, the disease was driven by a subset of T helper cells called Th2 cells, which mainly act to boost the production of antibodies and are important in allergies. The obese mice, however, had a greater number of Th17 cells, which are far more inflammatory than Th2 cells.

Why is this important? Some drugs for atopic dermatitis in humans target signalling molecules that are produced by Th2 cells, but Th17 cells produce a different set of signalling molecules. When the researchers tried using a similar drug to treat the obese mice, they found it actually made the condition worse. However, by boosting the activity of a protein called PPAR-gamma (which turns on key genes in Th2 cells), researchers were able to make the obese mice respond to the treatment.

There is some preliminary evidence that similar immune changes occur in obese humans with atopic dermatitis and asthma, so this study could have important medical implications.