Neuroscientist Mary Dallman does not want to replicate the whole human rat race -- just the part that stresses people out, fattens them up and causes a host of health problems.

Her current challenge is to produce a laboratory model -- and rats are the prime candidates -- that mimics a phenomenon observed in humans: stress sinks right down to the gut. A growing number of studies are documenting a link between chronic stress and abdominal fat. But the worry is about more than belt size and wardrobe. People -- the so called "apple-shaped" types -- who tend to accumulate their fat around the waist are at greater risk for diabetes, stroke and heart disease than those who carry excess fat in other parts of the body. "Abdominal obesity is a much bigger clinical problem than subcutaneous obesity," says Dallman.

Stress is nature's way of putting the body on alert, triggering a rush of hormones that aid the "fight-or-flight" response. But like many other things in life, too much of a good thing could be bad for your health. Under fear or stress, the body lets loose a one-two punch, pumping epinephrine, and then cortisol, to stimulate the heart to shift blood and energy to the muscles to take on an enemy or to run from it. But unlike epinephrine, which kicks in and dissipates quickly, cortisol works slower and lingers in the blood. Prolonged or chronic stress results in excess cortisol which diverts the body's resources, including fat, away from places like muscles and to the tummy.

Recent studies indeed have found higher levels of cortisol in apple-shaped persons, and Swedish studies nine years ago linked abdominal obesity not only to cardiovascular and other disease but also to psychological problems and symptoms of poor coping with stress. Another Swedish study, concentrating on middle-aged men with pot bellies, surprised stress experts and social and behavioral scientists. Potbellied men, who were lean everywhere else in the body, were more likely than their generally obese counterparts to have lower paying jobs, use sick leave, and suffer diseases such as peptic ulcer.

Dallman is now part of a new partnership between basic researchers and social scientists. Chronic stress, they believe, is a major contributor to the health problems of those at the lower rungs of the socioeconomic ladder. Unraveling the biological chain of events that go along with stress could lead to new stress-coping methods or medical interventions to control high blood pressure or lipid disorders. "None of these intervention strategies can be developed, and even fewer will be supported without basic research," says Nancy Adler, who directs UCSF's social and behavioral sciences programs and a new $4.6 million research effort, funded by the MacArthur Foundation, to examine socioeconomic status and health. (See Daybreak's "Top of the News.")

Dallman has studied rats for more than 30 years to understand, among many things, the physiology of stress, circadian rhythms, caloric intake, and the neural network that regulates hormonal and energy balance. She and six other resarchers in the laboratory have pampered rats, overfed and underfed them, subjected them to stress, and autopsied them for clues to how these systems work, or do not, in the human body.

Their studies have presented a picture of a tightly tuned association between feeding, metabolism and activity in the hypothalomo-pituitary-adrenal (HPA) axis -- one important arm of a two hormone system (the other is insulin) that signals and controls energy stores. Under normal conditions, the system balances our energy acquisition, or food intake, and storage of that energy or fuel in the body. Chronic stress activates the HPA, causing not only excessive production of cortisol but, unless feeding decreases, also insulin. Insulin, secreted when there are elevated levels of glucose in the blood, after eating, speeds the storage of the fuel molecules and also inhibits further food intake. But high levels of cortisol do just the opposite and stimulate the urge to eat. "Increases in the absolute levels of both hormones (cortisol and insulin) results in the remodeling of body energy stores -- away from muscle stores and toward fat stores, particularly abdominal fat stores," says Dallman.

Dallman's task now is to produce this effect in rats -- stress them, get them to eat, and to grow pot bellies. But how does one subject rats to the same kind of chronic stress experienced by people? It is not likely that you can give a rat a factory job and later lay him off. Nor can you induce rat parents to worry about how to send their rat kids to college.

In previous experiments, Dallman's laboratory has been able to induce stress in rats by confining them or exposing them to cold. Those stresses, however, suppressed their appetites and insulin secretion. "Rats normally don't eat or get fat with stress. People do, especially when they're depressed," she says.

There are ways to make laboratory rats fat -- removing a small area of their hypothalamus, for example, will make a rat eat just about anything. Then again, that is not what happens in stressed humans.

"We will try hard to set up a laboratory stress model that produces abdominal obesity, so we can then analyze the central nervous system to see how it happens," says Dallman.

If scientists can explain the mechanism and later interrupt the dangerous cycle of stress, overeating and fat accumulation around the abdomen, then the effort will be well worthwhile. But for now, they have a lot of food for thought.

--By Andy Evangelista

The above article will appear in the upcoming issue of the UCSF Magazine, available this month, in a section called "Science Stories."

1st appeared 4/15/97