Errant Enzyme Causes Big Bellies
Dec. 11, 2001 -- If you've been looking for something to blame that oversized gut on, researchers might just have found an excuse for you. It could be that darned overactive enzyme you've been cursed with.
Researchers at Beth Israel Deaconess Medical Center and Harvard Medical School have pinpointed an enzyme that, when overactive, causes a potbelly -- at least in mice.
In fact, a previous study from the University of Edinburgh (Scotland) showed increased enzyme activity in fat tissue of overweight humans.
"Hundreds of studies have led to the conclusion that any fat can be problematic, but it's much, much more dangerous when it's accumulated in the abdomen," senior author Jeffrey S. Flier, MD, says in a news release.
He adds that pound for pound, fat that builds up in the abdomen is much more likely to cause diabetes and heart disease. His research is published in the Dec. 7 issue of Science.
Flier and his colleagues looked at a stress hormone called cortisol -- the "fight or flight" hormone that kicks in during stressful situations. When the body produces excess cortisol, it tends to cause a build-up of belly fat. So the researchers thought this might be the reason why certain people tend to develop a "beer belly" while others don't.
They looked at an enzyme called 11-beta hydroxysteroid dehydrogenase type 1. This enzyme is able to increase the level of cortisol in fat cells without raising the level of cortisol in the blood.
The researchers genetically engineered mice that overproduce this enzyme. They made sure that the level of the enzyme was equivalent to the level previously found in the fatty tissue of overweight humans. As expected, the mice produced extra amounts of cortisol in their fat cells, but not in their blood.
The next step was to compare these mice to mice that produced normal amounts of the enzyme. Even when fed a low-fat diet, the genetically-altered mice developed a pot belly while the normal mice did not. The problem was even worse when the altered mice were fed a high-fat diet.
"We were surprised to find that it took only a modest increase in this enzyme to cause the mice to become ... obese," Flier says. The animals ate more than ordinary mice, and along with their pot bellies they developed diabetes, high cholesterol, and high blood pressure, he says.
The researchers hope to use the new knowledge to create an obesity treatment targeting elevated levels of this "beer belly enzyme."
"Obesity is a massive problem in our population," says Flier, who has been studying the molecular mechanisms of obesity for the past decade. It is linked to a huge burden of disease, he says, including high blood pressure, heart disease, cancers, reproductive problems, and diabetes. "In fact, an estimated 80% of diabetes [cases] would not exist in the absence of obesity," says Flier