A little-studied enzyme has been discovered to play a crucial role in adding fat to the body, scientists at the University of California, San Francisco report. The enzyme makes a promising target for fat-reducing drugs, the researchers said, since blocking its action causes people no harm.

The research, based on studies with human plasma, live mice and cell cultures, is being published in the March issue of Nature Cell Biology.

The enzyme, known as plasma kallikrein, triggers a physical breakdown of the environment immediately surrounding immature, or precursor, fat cells - the zone known as the extracellular matrix. The process frees the cells to balloon into mature fat cells or adipocytes. It is this transformation into full-blown orbs of fat, rather than an increase in the total number of cells, that is primarily responsible for adding body fat.

Underscoring the view that a cell's genes alone do not control its fate, the study shows that this key enzyme performs different tasks in different environments. It is produced in the liver and migrates continuously through the bloodstream. Until now, it was thought to be primarily involved in blood clotting and blood pressure maintenance. But when it enters tissues, it prepares the way for fat cells to develop.

Plasma kallikrein turns out to be a member of the "plasminogen activator" family, the researchers report, a small group of enzymes that unleash the potent bond-cleaving enzyme plasmin -- the prime mover in breaking down connective tissue and also clotting blood.

The better-known plasminogen activators, tPA and uPA, have been the subject of keen interest because they may facilitate invasion of tissues by cancer cells and metastasis to distant tissue sites. Yet efforts by other researchers to develop a cancer therapy by blocking these activators have so far proved disappointing, said Zena Werb, PhD, UCSF professor of anatomy, a member of the UCSF Comprehensive Cancer Center, and senior autho
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
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26-Feb-2001