Fat Mice Can’t Fight Infection

The increased cardiovascular health problems that are often an unfortunate side effect of obesity are already well documented. But researchers at the Goldman School of Dental Medicine have found that being extremely overweight or obese can lead to complications in oral health as well.

Salomon Amar, the SDM associate dean for research, has been performing experiments on mice that show obese animals have a slower inflammatory response when exposed to oral infection — meaning their systems are unable to fight off infection as well as those of lower-weight mice.

The paper describing Amar’s findings was published in the Proceedings of the National Academy of Sciences on Monday, December 10. Amar spoke with BU Today about his research, and what the findings mean for treating oral infection in humans.

BU Today: Can you explain the methodology involved in your research project?
Amar: The purpose of this study was to determine how an obese animal is sensing, recognizing, and dealing with infection. We had two groups, a group that took a normal-calorie diet, and another one that got probably 12 to 15 times the calories of the other group. At the completion of 16 weeks, we had animals that gained probably 50 percent of their body weight. At that time we made sure that they were not diabetic — to avoid complicating the system, and have clean answers as to the unique role of obesity into the system — and we started doing the experiments.

Then, we had groups that received just a general systemic infection, and groups that received an oral infection. And at that time, we started investigating how the obese animals were dealing with the infection. To our surprise, we noticed that they had difficulties in mounting an appropriate inflammation. So based on that, we have found that the animals have trouble eliminating the infection, and the end results of the infection are greater in the obese. When bacteria are left longer to linger, obviously damages are greater.

What are the practical applications of your results?
We will have to rethink our therapeutic approach with obese and overweight people. If they have a reduced inflammatory reaction, I’m not so sure we should use anti-inflammatories — rather, we should use a very targeted, antimicrobial therapy to eliminate lingering bacteria. That’s a first step. The second step is going to be investigating how we can boost the immune system, so that it’s not any more tolerant to the microorganisms. That has substantial ramifications from a treatment perspective — doctors will have to bearing in mind that infections and inflammation that will have potential consequences with wound healing.

Is this physiological effect reversible?
I’m not so sure that if you insult your system, it is going to become completely plastic and elastic, like a spring. There is a resilience factor, and beyond that I don’t think that it will come back completely to normal. We bought a treadmill for the mice, and they are running every day for an hour, to lose the weight. But you have to understand that even if it is completely reversible in the animal, it might not translate completely into the humans, because obesity is a chronic insult that you give to your body for a long period of time.

How will these results be used in future research projects?
Well, one question is whether the system is completely resilient enough to come back. When does the system recognize that it has been insulted enough, and it will not be plastic enough to go back to normalcy? Or, how can we bring back the system to a certain level? Other questions include whether these situations of immune dysfunction are involved in diabetes and cardiovascular complications.

In diabetes, you will not know whether the complication and consequences you are seeing are a result of your infection. It might be diabetic-related; it might be obesity-related. Maybe a combination of both. You will never know what’s what. That’s the reason we wanted, as best as we could, to separate the obesity from the diabetes, before they get to that level.

Robin Berghaus can be reached at berghaus@bu.edu. Jessica Ullian can be reached at jullian@bu.edu.