Obesity Beware!

Horwitz is studying leptin regulatory pathways in rats: The animals live in a 2-g (twice normal gravity) centrifuge in individual, free-swinging cages, for as long as eight weeks. Even though they're working against twice the gravity they're used to, the rats don't seem to mind. They move around, they groom themselves. If they're allowed, they'll even breed on the centrifuge, says Horwitz.

Living in double gravity naturally requires more energy. The rats were offered all the food they wanted, yet, at first, they ate less than they needed to maintain their body mass - much like astronauts in low gravity.

Horwitz and colleagues tested the rats (along with 1-g control groups) at 1, 2 and 8 weeks. During the first week, some of the rats' neuropeptides were mixed up. One, in particular, which stimulates feeding and therefore should have increased, actually went down.

By the eighth week, things were back to normal - almost. The animals produced the same amount of neuropeptides in both 1-g and 2-g habitats. Double-gravity rats were finally eating as much as they needed. But they remained lean: they never regained the fat they lost at the beginning of the study.

"That means that the pathway somehow was changed," says Horwitz. "The relationship between the amount of fat, and how much leptin was secreted, and the functioning of the feedback system is altered in high gravity."

Copyright: Mediagnost. All rights reserved. An artist's concept of the brain-body appetite control system.

Horwitz hopes to pinpoint the exact mechanisms by further testing the rats' genes: Each neuropeptide in the appetite feedback loop is produced or "expressed" by a gene that has been activated. Using a technology called DNA microarrays, Horwitz and colleagues examine thousands of rat genes at a time. They can see which genes have been activated, and how active they are.

Understanding the chemical pathways at this basic level could lead to "countermeasures," i.e., treatments to restore broken leptin regulatory systems.

Many researchers now believe that leptin's main role in humans is protecting against weight loss more so than weight gain. It makes sense: food surpluses are a relatively new phenomenon. Humans have evolved to withstand deprivation, not excess.

This makes leptin, potentially, even more important to astronauts: It's part of a regulatory pathway that keeps them from becoming too lean when stress, motion sickness and bland food take away their appetites.

Horwitz's research is important here on Earth, too. People with weight control problems like obesity may have defective leptin regulatory pathways: they tend to have plenty of leptin coursing through their bodies, but it does not cause them to eat less. The big question is why. Maybe their leptin receptors don't work well, or their neuropeptides aren't produced properly. Or it could be something else entirely.

Somewhere, along the pathway less travelled, lies the answer.