Tapping the Will Power of an Arctic Ground Squirrel

It's springtime, when Alaskans expose pasty white skin to the sun, illuminating the result of eight months of winter grazing. Too bad humans don't have the will power of arctic ground squirrels.

Ground squirrels, now stumbling out of their burrows after eight months of hibernation, are enjoying their first meals since September. Their first bite must be all the more satisfying because they resisted snacking all winter long. Although ground squirrels occasionally stir during hibernation, they tend to ignore the cached supply of seeds, berries and mushrooms in their burrow. A newly discovered hormone called leptin may be the root of this impressive ability to abstain.

Humans, who don't always possess a ground squirrel's ability to shun a midnight snack, are interested in leptin. Amgen, Inc., a California drug company, was so interested it paid $20 million to Dr. Jeff Friedman, the Howard Hughes Medical Institute, and Rockefeller University in New York City for an exclusive license to develop products made with leptin. The money was given to Friedman because he and other Rockefeller University researchers discovered an abnormal gene that produces faulty leptin in fat mice.

Leptin, from the Greek word "leptos" or "thin," is secreted by mammals' fat cells. The hormone is transported in the bloodstream to the brain, where leptin fits in brain cell receptors like a key fits in a lock. With enough leptin in place, the brain sends out a message: "We're full now. Put down that chocolate eclair!"

Leptin may be one of the keys to a "lipostat," a sort of thermostat that allows mammals to maintain a fairly constant body weight, said Bert Boyer, an assistant professor of biochemistry and molecular biology in the Institute of Arctic Biology at the University of Alaska Fairbanks.

For example, if a normal mouse is forced to overeat, it becomes obese. When the force feeding stops, the mouse won't eat as much as normal until it loses the excess weight it gained. Leptin may be the hormone flipping the switch on the lipostat to shut off the overfed mouse's appetite.

Boyer discovered that arctic ground squirrels (often seen hamming it up for tourists in Denali National Park) also are ideal subjects on which to study the effects of leptin on appetite.

Ground squirrels have an insatiable hunger during a pre-hibernation pigout from about the third week in July to the second week in August. Adult ground squirrels can double their body weight during this time as they put on fat to fuel them during the long slumber ahead, Boyer said.

To test the hormone's effectiveness, Boyer and biology graduate student Olav Ormseth implanted tiny leptin pumps under the skin of ground squirrels captured from the Alaska Range. The ground squirrels, who should have been eating everything in sight, didn't. instead, they cut their food intake by about 75 percent. Boyer thinks that perhaps leptin does more than just tell the brain the tummy's full, a hypothesis he'll explore with further research on ground squirrels. With funding from Amgen, Inc., and the National Institutes of Health, Boyer will study how leptin affects a ground squirrel's metabolism, or the process by which food is converted to energy.

Can increased quantities of leptin control human appetites? Maybe not. Medical researchers found that some obese people already have leptin levels 20 to 30 times higher than lean people, as was reported in the April 1996 Harvard Health Letter. Some researchers believe that obese people may have problems with leptin receptors in the brain; the "I'm full" message is reaching the brain, but it isn't being received.

Clinical tests are underway to determine leptin's effect on humans, but it will probably be six to 10 years before any weight-loss drugs based on the hormone become available, according to the Harvard Health Letter. Maybe arctic ground squirrels will help trim the fat off that time frame.