SOME CAN EAT, SOME CAN'T: Researchers show that serotonin controls feeding rate and fat storage independently, which may help explain why some people can eat what they want and never gain an ounce.
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Ever wondered why some people seem able to gobble down anything and still stay slim?

New research shows that the answer may lie in serotonin, a neurotransmitter, or chemical messenger produced by nerve cells. Scientists at the University of California, San Francisco, (U.C.S.F.) report in the journal Cell Metabolism that the nerve messenger, a known appetite suppressant, not only controls whether and how much you eat but, independent of that, also plays a role in what the body does with the calories once they're consumed.

"This may mean you could develop therapeutic strategies to manipulate fat metabolism (the rate at which food is turned into energy) independently of what you eat," says study co-author Kaveh Ashrafi, a U.C.S.F. physiologist.

Many weight-loss drugs now on the market are designed to increase serotonin levels, but they were believed to work by stemming appetite; the new research shows they may also work by speeding metabolism. That means, Ashrafi says, that treatments could be developed that target obesity, which has been linked to a slew of ills from diabetes to cancer, without necessarily suppressing appetite.

Ashrafi says he launched the study to determine why some people on diet drugs regained their weight after they stopped popping them, even if they did not increase their caloric intake.

"The assumption that body weight is simply a consequence of behavior is not exactly correct," he says. "It is the combination of behavior and the organism's propensity for what to do with nutrients it takes in," whether to store or use them.

Ashrafi, postdoc Supriya Srinivasan and their colleagues conducted their research on roundworms (Caenorhabditis elegans), which are genetically similar to mammals; all the fundamental mechanisms at work in the organism are also found in humans. The team created a number of mutant worms with engineered defects in proteins that serotonin controls; some of the proteins they tampered with affected appetite, others metabolism.

The researchers found that worms would alter their eating habits—although their fat content did not change—if they blocked proteins linked to appetite; if they disrupted proteins involved with metabolism, the worms would slim down even if they continued to down the same amount of food.

"We are not saying that feeding is not important for fat," Ashrafi warns. "What we've discovered here in the worm, at a molecular level, is the mechanisms that allow serotonin to have its appetite effect are different from those that control metabolism." He says this may explain why two individuals with similar eating and physical activity habits may have very different body weights—because their bodies process the food differently.

Ashrafi expects the findings to translate to humans. He says, however, that there is still much to learn about how the body regulates fat content. "The goal of this is not to say that here is a pill that will make people thin regardless of what they eat," he notes. "There is nothing in our study that argues against good nutrition and physical activity."