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Disabling enzyme allows mice to gorge without becoming obese, new study finds
Date:1/11/2009

Berkeley -- Researchers at the University of California, Berkeley, have identified a new enzyme that plays a far more important role than expected in controlling the breakdown of fat. In a new study to be published Jan. 11 in the journal Nature Medicine, researchers report that mice that have had this enzyme disabled remained lean despite eating a high-fat diet and losing a hormone that suppresses appetite.

"We have discovered a new enzyme within fat cells that is a key regulator of fat metabolism and body weight, making it a promising target in the search for a treatment for human obesity," said Hei Sook Sul, UC Berkeley professor of nutritional sciences and toxicology and principal investigator of the research.

Sul's research team includes the three co-lead authors of the paper, all from UC Berkeley's Department of Nutritional Sciences and Toxicology: Kathy Jaworski, former post-doctoral researcher; Maryam Ahmadian, graduate student; and Robin Duncan, post-doctoral fellow.

The enzyme in the spotlight, adipose-specific phospholipase A2 (AdPLA), is found in abundance only in fat tissue. AdPLA sets off a chain of events that increases levels of a signaling molecule called prostaglandin E2 (PGE2), which suppresses the breakdown of fat. Mice that have no AdPLA have lower PGE2 levels and a higher rate of fat metabolism.

"When levels of PGE2 are decreased because of the lack of AdPLA, fat breakdown proceeds unchecked, resulting in leanness even in animals that eat all day long," said co-lead author Duncan.

In the study, mice that had the gene for AdPLA expression knocked out were compared with a control group of normal mice. As soon as the mice were weaned at about 3 weeks of age, researchers began offering the two groups of mice an all-you-can-eat buffet of tasty, high-fat foods.

Notably, the enzyme did not appear to affect appetite since the two groups ate equivalent amounts. However, as the mice aged, t
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Contact: Sarah Yang
scyang@berkeley.edu
510-643-7741
University of California - Berkeley
Source:Eurekalert

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