In an Age of Obesity, Why Do Some Remain Thin?
Imagine two lab rats in their cages, one fat, one thin. The larger one pads around slowly or rests on the floor of wood shavings. She expends as little effort as possible to reach her water spigot, maybe even lying on her back and gripping it with pink paws so that the water drips into her mouth.
Her thin neighbor, on the other hand, darts around the cage, whiskers twitching, eyes alert. Taken out and placed on a treadmill, she picks up the pace and overtakes the top of the belt.
The tale of two rats, in short, is the story of why some rats (and people) do not gain weight while others do. It suggests a “chicken and egg” question of which comes first -- obesity or inactivity. Colleen Novak, Ph.D., assistant professor of biological sciences, is seeking the answer by comparing the brain function of rats that are bred to be either active or inactive.
Her work contributes insights to a complex problem that scientists are tackling – what causes obesity -- a growing public health problem -- and how to prevent and treat it. As many as one third of adults in the U.S. are obese and another third are overweight.
SOME RATS HAVE “HOT LEGS”
One type of rat that she studies is bred to have naturally high aerobic capacity -- to be a runner. The other has the couch-potato genes. Even before they take up a fitness routine, the two types display the profile and behavior associated with a runner (thin, active) or a relaxer (obese, sluggish).
Novak’s research looks at how their brain function differs: how certain neuro-peptides, which are short proteins in the brain, are released and how they act on brain receptor “on” cells that give the signal to be active. This melanocortin system, as it is known, operates differently in thin rats and fat rats.
Looking at specific regions and specific receptors, she has shown that a receptor in a particular region of the brain can increase activity in a highly active rat but not in its inactive counterpart: the thin rats are more receptive to the signal to be active. On a rat treadmill, the runner rats burn more calories for their size than the couch potatoes. They have what researchers in her lab call “hot legs,” measured by tiny transponders that that calculate the heat coming off their leg muscles.
When the melanocortin system is stimulated with drugs, the thin rats burn more calories than the fat rats. This shows that the brain controls how much energy is burned when the rat is active, Novak said.
Her research looks at how the system does this: how it changes the muscle and how that differs in fat and thin rats. In answer to the “chicken and egg” question, she has found that fat rats move less, but their inactivity is not linked to their weight but to their brain function.
ACTIVITY AND OBESITY
The causes of obesity range from genetics to epigenetics – what is passed on to a fetus from its mother’s diet and activity – to the environment, Novak noted. While genes play a role in obesity, they are rarely the only cause. Diet and activity affect weight, too.
Novak herself models the behavior of the thin phenotype. Behind the standard-issue desk on her office is a treadmill desk, a trend started by her postdoctoral adviser at the Mayo Clinic, Dr. James Levine. Studies have shown that prolonged sitting can contribute not just to obesity, but also to muscle degeneration, an increased risk for cardiovascular disease, and early death.
Before conducting research at Mayo, Novak earned her Ph.D. in neuroscience at Michigan State University. Her research is funded by the National Institutes of Health and the American Heart Association.
Obesity is a mostly modern phenomenon, becoming more common as people expend less energy in their work, she said. The link of inactivity and obesity to a host of other health problems – cardiovascular disease and diabetes among them – is seen even in the lab rats she studies.
The research in her lab will add to our knowledge of how, in a sedentary and obesity-prone society, some people remain resistant to weight gain.
Hear more: Colleen Novak podcast (link)