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Friday January 11 5:30 PM ET
By Merritt McKinney
NEW YORK (Reuters Health) - A couple of years ago, scientists discovered that a compound called C75 could suppress the appetite of obese mice. Now researchers report that they have moved a step closer to understanding how C75 works.
The research eventually may lead to a better understanding of how appetite is regulated in people and, perhaps, to drugs that keep people from eating too much, the study's lead author told Reuters Health.
C75 blocks an enzyme called fatty acid synthase, and causes both normal and obese mice to eat less and lose weight.
To investigate how C75 works, Dr. M. Daniel Lane and colleagues at Johns Hopkins University School of Medicine in Baltimore, Maryland, monitored appetite signals in the brains of a group of mice that fasted for a day and another set that was given C75. Both groups included obese and normal, or lean, mice.
Neither group of mice ate during the day, but Lane's team detected differences between the groups in appetite signaling.
In an interview with Reuters Health, Lane explained that fasting usually increases levels of two brain chemicals, AgRP and NPY. These so-called neurotransmitters, which originate in a brain region called the hypothalamus, send instructions to eat, he said.
Levels of two other brain messengers, CART and POMC, which send signals to stop eating, usually decline during fasting, according to Lane.
C75 seems to disrupt this process, the investigators report in the January 8th issue of the Proceedings of the National Academy of Sciences (news - web sites).
In both lean and obese mice, C75 kept levels of NPY and AgRP--the chemicals that encourage eating--from rising. The compound also blocked the decline of CART and POMC in lean mice. In fact, levels of these appetite-suppressing molecules increased slightly in lean mice treated with C75.
In contrast, C75 did not have an effect on CART and POMC in obese mice. Both lean and obese mice ate less and lost weight after receiving C75, the report indicates.
Referring to C75, Lane said, ``We are looking at the effect of this drug on neuropeptides that either cause animals to eat or to reduce their food intake.'' The researchers still do not know all the answers to how C75 works, Lane noted, but he said, ''We're getting closer.''
The effects of C75 may not be permanent, Lane told Reuters Health. In recent experiments, he and his colleagues found that lean mice become resistant to the appetite-suppressing effects of C75. After eating less for a few days, they begin to eat normally, he explained.
But Lane noted, ``That's not the case with the obese mouse.'' He and his colleagues plan to study the long-term effects of C75 on obese mice.
``We predict that they will become resistant to C75 once they become lean,'' Lane added.
The research eventually could lead to new treatments for obesity, Lane suggested, but he stressed that ``there is a lot more that has to be done'' before C75 can be tested in people.
Lane said that a molecule called malonyl CoA may be responsible for the changes in the levels of appetite-regulating brain chemicals. Normally, fatty acid synthase--the enzyme C75 blocks--transforms malonyl CoA into a fatty acid. So when a mouse is given C75, this process is blocked, which causes levels of malonyl CoA to rise.
Lane's team suspects that the hypothalamus may interpret the rise in malonyl CoA as a sign that the mouse is eating enough.
One of Lane's co-authors works for the Japanese company Yamanouchi Pharmaceuticals. The Yamanouchi USA Foundation provided partial funding for the research.
SOURCE: Proceedings of the National Academy of Sciences 2002;99:66-71.
By Merritt McKinney
NEW YORK (Reuters Health) - A couple of years ago, scientists discovered that a compound called C75 could suppress the appetite of obese mice. Now researchers report that they have moved a step closer to understanding how C75 works.
The research eventually may lead to a better understanding of how appetite is regulated in people and, perhaps, to drugs that keep people from eating too much, the study's lead author told Reuters Health.
C75 blocks an enzyme called fatty acid synthase, and causes both normal and obese mice to eat less and lose weight.
To investigate how C75 works, Dr. M. Daniel Lane and colleagues at Johns Hopkins University School of Medicine in Baltimore, Maryland, monitored appetite signals in the brains of a group of mice that fasted for a day and another set that was given C75. Both groups included obese and normal, or lean, mice.
Neither group of mice ate during the day, but Lane's team detected differences between the groups in appetite signaling.
In an interview with Reuters Health, Lane explained that fasting usually increases levels of two brain chemicals, AgRP and NPY. These so-called neurotransmitters, which originate in a brain region called the hypothalamus, send instructions to eat, he said.
Levels of two other brain messengers, CART and POMC, which send signals to stop eating, usually decline during fasting, according to Lane.
C75 seems to disrupt this process, the investigators report in the January 8th issue of the Proceedings of the National Academy of Sciences (news - web sites).
In both lean and obese mice, C75 kept levels of NPY and AgRP--the chemicals that encourage eating--from rising. The compound also blocked the decline of CART and POMC in lean mice. In fact, levels of these appetite-suppressing molecules increased slightly in lean mice treated with C75.
In contrast, C75 did not have an effect on CART and POMC in obese mice. Both lean and obese mice ate less and lost weight after receiving C75, the report indicates.
Referring to C75, Lane said, ``We are looking at the effect of this drug on neuropeptides that either cause animals to eat or to reduce their food intake.'' The researchers still do not know all the answers to how C75 works, Lane noted, but he said, ''We're getting closer.''
The effects of C75 may not be permanent, Lane told Reuters Health. In recent experiments, he and his colleagues found that lean mice become resistant to the appetite-suppressing effects of C75. After eating less for a few days, they begin to eat normally, he explained.
But Lane noted, ``That's not the case with the obese mouse.'' He and his colleagues plan to study the long-term effects of C75 on obese mice.
``We predict that they will become resistant to C75 once they become lean,'' Lane added.
The research eventually could lead to new treatments for obesity, Lane suggested, but he stressed that ``there is a lot more that has to be done'' before C75 can be tested in people.
Lane said that a molecule called malonyl CoA may be responsible for the changes in the levels of appetite-regulating brain chemicals. Normally, fatty acid synthase--the enzyme C75 blocks--transforms malonyl CoA into a fatty acid. So when a mouse is given C75, this process is blocked, which causes levels of malonyl CoA to rise.
Lane's team suspects that the hypothalamus may interpret the rise in malonyl CoA as a sign that the mouse is eating enough.
One of Lane's co-authors works for the Japanese company Yamanouchi Pharmaceuticals. The Yamanouchi USA Foundation provided partial funding for the research.
SOURCE: Proceedings of the National Academy of Sciences 2002;99:66-71.
