Harvard Scientists Find Enzyme Causing Obesity Diseases

After 30 years of head-scratching, scientists have finally found the answer to the question, “Why apples and not pears?”

But they’re not talking about grocery lists.

A group of scientists from Harvard and Edinburgh, Scotland has finally identified the enzyme that makes those who carry weight around their waists—the so-called “apple-shaped” — more susceptible to obesity-related illnesses such as heart disease and diabetes than their hip-weighted, “pear-shaped” counterparts, according to a report in Friday’s issue of Science.

The enzyme is 11ß hydroxysteroid dehydrogenase type 1 (11ß HSD-1), which works to recycle a steroid stress hormone called cortisol. Though necessary for the body to maintain strength, cortisol may cause weight gain, high blood pressure and diabetes when produced by the body in excessive amounts.

Inspired by previous studies that revealed the enzyme’s high activity in abdominal fat, endocrinologist Dr. Jeffrey S. Flier, professor of medicine at Harvard Medical School and faculty dean for academic affiliation at the Beth Israel Deaconess Medical Center, decided to engage in further research.

The question was, if a mouse could be made to produce excessive amounts of the enzyme, would it also develop an apple-shaped body and its ill effects?

In the experiment, that was exactly what happened. The fruits of Flier’s year and a half long study at Beth Israel Deaconess Medical Center revealed that not only did the mice grow in the same fashion as overweight apple-shaped people, but in adulthood they also developed early symptoms of heart disease and diabetes.

Until now, only correlative evidence has linked visceral fat in the abdominal area with obesity-related disease, said Hiroaki Masuzaki, a visiting researcher at Beth Israel and a member of Flier’s team. Until Flier’s experiment, no one knew precisely why this correlation occurred, Masuzaki said.

“Having been in the field for a while, I do have a feeling that this one is going to have some significance,” Flier said.

There is still much work to be done. Although genetic evidence is definite in rodents, it still remains to be tested on humans, Masuzaki said. Flier speculated that controlled clinical trials will begin in two and a half to three years.

One moderately successful anti-diabetic drug currently on the market partially suppresses the enzyme, Flier said.

But the type of drug that will hopefully result from this new discovery, Flier said, will bind directly to the enzyme and inhibit it, yielding more successful results.

However, these new drugs will not put an end to all cases of diabetes and heart disease. Flier noted that the enzyme cannot be blamed for all such cases, and that each instance must be handled individually.

Nor is it clear why some people have greater quantities of the enzyme. That, Flier said, is his next project.