Enzyme linked to Obesity

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I thought this was pretty interesting...

all the best,

lap ds with gallbladder removal

January 25, 2001

Dr. Gagner/Mt. Sinai/NYC

10 months post-op and still feelin' fabu

preop: 307 lbs/bmi 45

now: 198 lbs/bmi 28/size sweet 16 but squeezin' into a 14! LOL

Enzyme may be target for future obesity drug-study

By Maggie Fox, Health and Science Correspondent

WASHINGTON, Dec 6 (Reuters) - A stress-related hormone may hold the key to

the most dangerous type of obesity -- the so-called apple-shaped syndrome in

which people get fat bellies and often diabetes, high blood pressure and

heart disease, researchers said on Thursday.

They hope drugs can be designed that can help control the hormone and perhaps

stave off the dangerous results of such obesity.

" This has the flavor of something that may be a mechanism that contributes

importantly to typical obesity, " said Dr. Flier of Harvard Medical

School and Beth Israel Deaconess Medical Center in Boston, who led the study,

published in Friday's issue of the journal Science.

More than 60 percent of Americans are overweight and more than a quarter are

obese, meaning they have a high risk of health problems linked to their

weight, according to the U.S Centers for Disease Control and Prevention

(CDC).

Many studies have shown that it is often easy to tell who is most at risk by

measuring waist circumference. This points to visceral fat, a build-up of fat

inside the abdomen that is associated with the most dangerous effects of

obesity.

People with a rare disease called Cushing's syndrome have too much abdominal

fat as well as diabetes and high blood pressure, Flier said in a telephone

interview, but the condition looks a lot like common obesity.

" This obvious fact caused many scientists and companies to wonder if it is

possible that many patients with obesity have a mild form of Cushing's

syndrome, " he said. " That question has been asked over and over again. "

The answer, however, is no. Cushing's is characterized by a high level of the

stress hormone cortisol in the blood, and most obese people have normal

levels.

ENZYME REACTIVATES STRESS HORMONE

Researchers studied the role of stress hormones and enzymes that affect them.

One of particular interest was HSD-1. Cortisol is deactivated by several

enzymes, but HSD-1 can reactivate it inside a cell.

Flier saw work by British researchers that suggested this could happen only

in fat cells. " They raised the idea that you make too much (cortisol), but

only in the abdominal fat cell itself, " he said.

If this was happening, it would explain why some obese people have the extra

abdominal fat without extra cortisol in their blood.

" The way I went about proving it with my colleagues was to create a genetic

experiment and take a normal mouse, force the mouse to have more than normal

level of this enzyme activity, but only in its fat cells, " said Flier, who

worked with Janice Paterson and colleagues at the University of Edinburgh.

" We got exactly, even more than we bargained for. "

The mice were fat and ate more than normal mice. " On top of that they

developed diabetes, they developed high lipids in the blood (high

cholesterol). They also developed high blood pressure, " Flier said.

At the same time, British researchers reported they found the more fat people

had in their bodies, the higher the level of the same enzyme, HSD-1, in their

fat cells. The enzyme was working only in the fat cells, not in the rest of

the body. It was like a localized version of Cushing's syndrome.

" We don't know why some people have more of this enzyme activity than

others, " Flier said, adding that he thought it could be a combination of

genes, diet and exercise.

The immediate thought was that if a drug could stop the effects of the

enzyme, people with the apple-shaped obesity problems could be helped.

Flier said several pharmaceutical companies, which he declined to name, are

already working on such a drug.

He said another British team had genetically engineered mice that do not make

any HSD-1 and they are healthy.

" You don't need the enzyme to live, which is good, and what is more, they

reported ... when you put them on a high-fat diet, which normally makes an

animal a little bit diabetic, those mice don't get diabetes. "

Flier said he did not believe HSD-1 would turn out to be like another hormone

linked with obesity -- leptin.

Obese rats lost weight when injected with leptin, raising hopes that leptin

might be an easy diet pill. But obese humans were found to have above normal

leptin levels and giving them additional leptin had little or no effect on

their weight.

Flier says this one feels different. " Even though I can't prove it, I have a

personal feeling this one will lead to something, " he said.

11:30 12-06-01

Copyright 2001 Reuters Limited. All rights reserved.