Put a mouse or a rat under stress and what does it do? It stops eating. Humans should be so lucky. When people suffer nontraumatic stress they often head for the refrigerator, producing unhealthy extra pounds.
When Syrian hamsters, which are normally solitary, are placed in a group-living situation, they also gain weight. So scientists at the Center for Behavioral Neuroscience at Georgia State University are using hamsters as a model for human stress-induced obesity. They want to begin unraveling the complex factors that lead people to eat when under stress and hope that the information can eventually be used to block appetites under this common scenario.
The study, “Social defeat increases food intake, body mass, and adiposity in Syrian hamsters,” by Michelle T. Foster, Matia B. Solomon, Kim L. Huhman and Timothy J. Bartness, Georgia State University, Atlanta, appears in the May issue of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology published by The American Physiological Society.
In the study, the researchers look at nontraumatic stress - the stress we experience in everyday life, such as getting stuck in traffic or trying to complete a major project at work. It is distinct from traumatic stress, such as suffering the death of a loved one. Traumatic stress typically dulls the human appetite, said Bartness, the study’s senior researcher and an authority on obesity.
In the U.S., where food is plentiful and relatively cheap, overeating can be difficult to control. Stress-related overeating is more difficult to control than the overeating that people do just because food tastes good and is available, Bartness said. If scientists could learn how to reduce the urge to eat in the face of stress, it could improve the health of a lot of people. And that was the point of this study.
The researchers used Syrian hamsters, the kind commonly found in pet stores. They set up a situation in which subordinate hamsters would suffer a “social defeat” at the hands of a dominant hamster. The researchers wanted to see if the defeated hamsters would eat more and gain weight under the stress, just like a human. Mice and rats eat less and lose weight when subjected to a similar stress, making them a poor subject for human stress-induced obesity research.
The study asked three questions:
- Does repeated social defeat increase food intake, weight and fat in hamsters?
- If so, how many defeats are necessary?
- Do intermittent (unpredictable) defeats increase fat and food intake more than consecutive (predictable) defeats, as is true in humans?
To answer these questions, the researchers placed an 11-week-old hamster (the subordinate intruder) into the cage of an older and larger hamster (the dominant resident). The intruder remained in the aggressor’s cage for seven minutes per trial. The situation set up a clear dominant versus subordinate situation between the hamsters, the authors explained.
“Hamster aggression is highly ritualized, with dominance or submission generally established within the first minute and maintained thereafter through social signals and social communication between the opponents,” the authors wrote. The intensity of most agonistic encounters was moderate, with some chasing and biting, but with no actual tissue damage.
A trained observer recorded submissive behaviors and also ensured that no harm came to either of the hamsters, which normally live alone. Because the smaller hamster was the intruder, the outcome of the dominance/submissive tussle was a foregone conclusion.
The researchers found that, as a result of the stress of being placed in the home cage of a larger resident, intruder hamsters subsequently:
- ate significantly more
- gained significantly more weight
- gained significantly more fat, including visceral fat
These results occurred when the intruder hamsters were placed in the foreign cage as few as four times, a total of 28 minutes, over the 33-day experiment, Bartness explained. Hamsters that were placed in the situation only once during the experiment did not eat more or gain weight compared to a control group. In addition, the intruder hamsters that were placed in the cage intermittently (at unpredictable times) showed comparable weight and fat gain compared to those placed in a foreign cage consecutively (at regular times).
However, while the intermittent group increased on all measures of fat gain, the consecutive group increased on only two of the fat measures. Still, this was an unexpected result.
“In humans, unpredictable [stress] events are more aversive than predictable events, causing greater alterations in homeostasis and thus increased stress,” the authors wrote. “In addition, previous research suggests that unpredictable events cause greater activation in brain regions responsible for fear and anxiety in laboratory rats and reduction in immune function compared with events that are predictable.”
Syrian hamsters provide a good model for obesity research, not only because they eat more and gain weight, but because, like humans, they add fat to their abdomens - visceral fat. Visceral fat is particularly unhealthy because it affects the internal organs and is associated with diabetes, cancer and other serious illnesses, Bartness said.
Bartness’ team began a second study to determine whether other stressors, such as a mild foot shock, produce the same effect as the social defeat model; and whether the dominant hamsters gain weight and fat as the result of the intrusion of the submissive hamsters.
Another line of inquiry would be to compare mice and rats to hamsters. Humans and hamsters, which eat more under stress, share the same predominant stress hormone, cortisol, noted Bartness, Rats and mice, which eat less under stress, have a different primary stress hormone, corticosterone. This raises the question of whether stress-induced increases in cortisol play a more important role in the desire to eat and weight gain compared to corticosterone.
Researchers will also want to know if drugs can block stress-induced obesity, for example, by blocking the release of the stress hormone, corticotrophin releasing factor (CRF), or by blocking the body’s CRF receptors, Bartness said. CRF, also sometimes referred to as corticotrophin releasing hormone, produces the body’s “fight or flight” response under stress and helps kick off a cascade of physiological responses.
“There are a whole suite of physiological responses that occur as a result of stress,” Bartness said. It will take time to unravel all these physiological responses and to use that knowledge to block stress-induced obesity. It may even turn out that the reactions are too complex to easily block, he said.
Revision date: July 5, 2011
Last revised: by Jorge P. Ribeiro, MD