NPY-related.....
infobeat.com
06:03 PM ET 06/29/00
Tests Reveal Possible Fat Fighter
By LAURAN NEERGAARD=
AP Medical Writer=
WASHINGTON (AP) _ Scientists were testing a possible cancer
treatment when they spotted a side effect that might prove rather
valuable: The experimental drug made mice lose a dramatic amount of
weight, without apparent side effects.
Just 20 minutes after taking the chemical, the rodents'
appetites were wiped out.
The discovery indicates scientists may be able to regulate a
major pathway in the brain responsible for appetite and
fat-building. The chemical apparently fooled the brain into
thinking the mice had eaten, so their metabolisms never slowed and
they burned fat, researchers report in Friday's edition of the
journal Science.
``This is a real trick. The mice drop their weight like a stone,
losing 25 percent of their body mass in a couple of days,'' said
Dr. Frank Kuhajda, who led the research team at Baltimore's Johns
Hopkins University that produced the chemical, code-named C75.
No one yet knows if C75 would work in humans, experts caution.
More animal research is needed before dieters could even test it.
But, the Hopkins discovery is ``extraordinarily intriguing and
provocative,'' said Denis McGarry, an expert on fat metabolism at
the University of Texas Southwestern Medical Center in Dallas. If
confirmed, he said, ``it would obviously have a profound impact on
the field of obesity research.''
Doctors have long hoped for better weight-loss treatments. Over
half of all Americans are overweight, and about one-quarter are
obese, government estimates show.
At issue is ``fatty acid synthase'' or FAS, an enzyme system
pivotal for turning carbohydrates into the building blocks of fat.
Surprisingly, in the early 1990s scientists discovered cancer
cells use FAS to produce their own fat for fuel, Kuhajda said. No
one knows why. But the Hopkins researchers created a FAS blocker to
see if it could fight cancer. In mouse testing, this so-called C75
made cancer cells die without harming nearby normal cells, he said.
But the mice all had a stunning side effect: They stopped eating
and dramatically lost weight until the drug wore off.
Weight loss in a cancer patient is a serious problem, so the
puzzled scientists began hunting an explanation.
It turns out that production of a brain chemical called
neuropeptide Y _ a well-known appetite regulator _ plummeted in the
C75-treated mice. Normally when animals fast, neuropeptide Y
sharply jumps and appetite consequently increases. But the C75
prevented that, fooling animals into thinking they were fed,
Kuhajda said.
How? To build fat, FAS uses another molecule called malonyl-CoA.
Blocking FAS didn't stop the body's normal production of that
molecule. Instead, malonyl-CoA just piled up without that next step
in the fat-building assembly line. High levels of the molecule
somehow signaled the brain not to produce neuropeptide Y, Kuhajda
said.
C75 didn't permanently harm the appetite system. When scientists
injected C75-treated mice with neuropeptide Y, they immediately
stuffed themselves. When C75 wore off, they ate normally and
regained weight.
But C75 had another important benefit, the researchers reported.
One reason dieting is so hard is that fasting slows metabolism.
Metabolism didn't seem to slow in the C75-treated mice, however _
they lost 45 percent more weight than untreated mice deprived of
food.
The Hopkins researchers are pursuing C75 as a possible cancer
treatment, figuring appetite suppression isn't an insurmountable
side effect. But the newest findings ``give us some hope'' of a new
way to fight obesity, too, Kuhajda concluded. |
