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A New Target For a Fat-Fighting Drug

Blocking enzyme might flush fats from body, researchers say

THURSDAY, Nov. 18, 2004 (HealthDayNews) -- A newly discovered enzyme that plays a major role in fat metabolism could be a target for a different kind of weight-loss drug, Austrian researchers report.

The enzyme, designated ATGL, starts the process by which the body metabolizes fats, using them for energy. Blocking ATGL's activity could mean that more fat would exit the body rather than being stored in what scientists call adipose tissue, says a report in the Nov. 19 issue of Science. The research was carried out at the University of Graz Research Institute of Molecular Pathology.

The enzyme has been identified in mice, said study author Rudolf Zechner, a scientist at the institute. "Whether such an inhibition could be beneficial for patients with obesity and type 2 diabetes remains to be determined," Zechner said. "Right now we are at the stage of optimistic speculations."

ATGL is a member of a family of enzymes called lipases that act to metabolize fats. Until now, only one other lipase has been known to play a role in human fat metabolism. That enzyme, hormone-sensitive lipase (HSL), was discovered a number of years ago. The drug Xenical, which blocks the activity of HSL, is marketed by the Roche Pharmaceuticals for weight reduction.

Asked to assess the Austrian report, Terence J. Hurley, a Roche spokesman, said, "It really wouldn't be appropriate for us to comment on this."

Blocking the activity of ATGL might be a more effective strategy because mouse experiments indicate that HSL blockage results in unwanted accumulation of fats called diglycerides, Zechner said.

"Inhibition of ATGL, which is much more a triglyceride than diglyceride lipase, might not show this unwanted side effect," he said. "To make a more competent judgment, however, it is absolutely necessary to analyze ATGL knockout mice."

A knockout mouse is one that has been genetically engineered to lack a specific enzyme.

The Austrian researchers are working to get a better understanding of exactly what ATGL does, Zechner said, with a marketable product definitely in mind.

"As soon as these results support our present view that inhibition of ATGL could be beneficial for lipid [fat] and energy metabolism, we expect drug companies to develop specific ATGL inhibitors," he said.

More information

The American Academy of Family Physicians offers a doctors-eye view of where a lipase inhibitor fits in the weight reduction picture.

SOURCES: Rudolf Zechner, Ph.D, scientist, University of Graz Research Institute of Molecular Pathology, Austria; Terence J. Hurley, spokesman, Roche Pharmaceuticals, Nutley, N.J.; Nov. 19, 2004, Science
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