Lose Weight Now, Ask Mice How

To regulate the amount of fat that swaddles the body, the body has to tell the brain how much food it needs. Now researchers report that a molecule that helps synthesize fat also tells the brain when to feel the munchies. Blocking the enzyme, they found, causes the animals to lose weight.

The discovery was sparked by earlier work on an enzyme that puts together the building blocks of fat. Researchers have been trying to find a way to block this enzyme, called fatty synthase. Working with pathologist Francis Kuhajda of Johns Hopkins University, Craig Townsend synthesized a promising inhibitor called C75.

Kuhajda and his colleagues then tested C75 on mice. These animals ate just 10% of the food their untreated littermates consumed, and their body weights dropped by almost a third. When the diets were restricted, mice treated with C75 lost 45% more weight than littermates eating the same amount. This suggests that C75 works on metabolism as well as appetite, the team reports in the 30 June issue of Science. The signal that tells the brain to lessen the appetite seems to be a build up of an ingredient of fat, called malonyl-CoA. When the researchers prevented the body from making malonyl-CoA, the C75 doesn't have as big an effect.

"This is provocative and exciting, and I think we will see an avalanche of work to see if it has validity," says Dennis McGarry, a fat metabolism researcher at the University of Texas Southwestern Medical Center in Dallas. There's still the multimillion-dollar question of whether the drug or chemical derivatives of it will ever prove useful in curbing human obesity. "That would be the hope," McGarry says. He cautions that such a scenario is still a long way off, especially as C75 is rather draconian in its suppression of appetite.