Single enzyme may be linked ...( BOSTON The increased activity of a sin...)

BOSTON The increased activity of a single enzyme in fat cells may be a common cause of obesity and obesity-linked diseases, including diabetes, according to an animal study conducted by researchers at Beth Israel Deaconess Medical Center and the University of Edinburgh and published in the Dec. 7 issue of Science. The findings could eventually pave the way for future drug development to curb visceral obesity the beer belly fat concentrated in the abdomen.

Hundreds of studies have led to the conclusion that any fat can be problematic, but its much, much more dangerous when its accumulated in the abdomen, notes lead author Jeffrey S. Flier, M.D., an endocrinologist at Beth Israel Deaconess Medical Center and the George C. Reisman Professor of Medicine at Harvard Medical School. Pound for pound, intra-abdominal fat is much more likely to cause diabetes, heart disease and other diseases that make up the metabolic syndrome.

To identify the molecular mechanism behind the accumulation of the excess abdominal fat, Flier and his colleagues looked at the role of the glucocorticoid hormone cortisol, the fight or flight hormone that helps people survive stressful situations. Observations of patients with the endocrine disorder Cushing's syndrome who have too much cortisol in their blood had shown that they develop increased intra-abdominal fat as well as other metabolic symptoms. This led Flier to hypothesize that obese patients who don't typically have increased blood cortisol levels may be producing increased amounts of cortisol in their fat cells.

To test this hypothesis, Flier and his colleagues studied the enzyme 11beta hydroxysteroid dehydrogenase type 1 (11 beta HSD-1), which has the unique ability to produce cortisol in cells that are not normally associated with cortisol production. This enzyme is known to be present in fat cells.

The researchers created a group of transgenic (Tg) mice that overproduce 11 beta HSD-1 in roughly t
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Contact: Jerry Berger
jberger@caregroup.harvard.edu
617-632-8062
Beth Israel Deaconess Medical Center
6-Dec-2001

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