Overweight people respond differently to certain drugs than lean people, study finds

During his graduate studies at Salk Institute for Biological Studies Dr. Sagar Bapat faced a puzzling anomaly. On one hand, he found that when mice contracted a common form of allergic skin inflammation—called atopic dermatitis—drugs targeting the immune system quickly healed their itchy, thickened skin. On the other hand, when obese mice were treated using the same drugs their skin condition actually became worse.

Why was there a difference? Why did obesity change the effectiveness of the medication?

Bapat, now a member of the faculty at the University of California in San Francisco, set out to find the answer. He was assisted by a research team at the university as well as members from Gladstone Institutes and the Salk Institute.

They expected to see a greater degree of the same kind of inflammation in the obese mice, he explains. Instead, the researchers saw a completely different kind of inflammation.

Their research revealed that the reason for the changed reactions to the drugs was that obesity can rewire the way in which the body’s immune system works. Being overweight altered the molecular workings behind allergic inflammation in mice, they explained.

Humans, too

What is more, they found that it operates that way in humans, too. 

The team analyzed information from people with allergic diseases, including 59 who suffered from the skin ailment atopic dermatitis. They also looked at the records of hundreds of people with asthma, which is also a condition that involves the immune system.

Although the team members say more studies are needed on people, the data shows that in both mice and humans obesity causes a change in the cells that cause the inflammation. This switch in the T cells has consequences for the study of  allergic disease and the effectiveness of drugs that target those cells that are associated with inflammation, they explain.

Identical twins could respond differently

The studies suggest that identical twins can show up at a hospital with the same disease, but if one is lean and the other is obese, it is possible that the same drug will work on only one of them and not on both, Bapat says.

The result: Armed with this knowledge, physicians should quickly and safely be able to treat asthma and allergies in people who are obese. So much so that drugs already approved by the Federal Drug Administration (FDA) might be effective when used in combination on certain people, the researchers point out. 

The findings show that differences in our metabolic states can play a major role when it comes to inflammation and how drugs might be able to improve our health, says Dr. Ronald Evans, also a senior author of the study and director of Salk’s Gene Expression Laboratory and the March of Dimes Chair in Molecular and Developmental Biology at Salk.

Obesity is increasing around the world

The findings are significant as we are living at a time when the incidence of obesity is growing around the world, says Dr. Alex Marson, director of the Gladstone-UCSF Institute of Genomic Immunology who was a senior author of the study.

Changes in body composition and diet can affect the immune system, he explains. We therefore have to consider how diseases involving the immune system might be different between those who are obese and those who are not.

A recent study published in the New England Journal of Medicine estimated that about half of all adults in the United States will be classified as being obese by 2030. Research also has found that obesity—which also has been classified as a chronic state of inflammation—changes the immune system in a variety of ways.

Clinicians report that those people who are obese will often appear to have different courses of disease—including allergies, infections, and cancer—and therefore will respond differently to treatments.

The new research takes those observations a big step forward.

The study is published in the journal Nature.