Hormone research draws attention

by Janice Hamilton

Concordia graduate student Stephanie Fulton is off to a promising career start with an article published in the January 7 issue of the highly respected journal Science. It describes the research she did for her Master's thesis in experimental psychology on leptin, a recently discovered hormone that helps the body strike a balance between obesity and emaciation.

"Leptin is a hot topic," said Peter Shizgal, Director of Concordia's Centre for Studies in Behavioural Neurobiology (CSBN), who co-authored the paper along with Fulton and Associate Professor of Psychology Barbara Woodside.

"Leptin is secreted by fat cells, and travels in the blood to act on various targets, mainly the brain," Fulton explained. "When it binds to receptors on brain cells, a series of neurochemical changes occur which have been shown to be related to feeding and body weight regulation."

Many scientists are interested in leptin because of its importance in basic biology and the possibility that it may some day help combat obesity.

Several studies have demonstrated that when leptin is injected into obese, mutant rats that can't make this protein themselves, they eat less and get thinner, but no one knew exactly why. "We tackled the question of what goes on between the molecule and the behaviour," Shizgal continued. "Our goal was to learn about the brain mechanisms responsible for the decrease in food intake produced by leptin."

On the basis of the results, the researchers speculate that two complementary effects of leptin are involved. Leptin may decrease the attractiveness of food, while also increasing the value of activities incompatible with feeding.

First, Fulton replicated an experiment originally carried out by a New York University researcher. She restricted the food given to a group of chubby, middle-aged rats for several weeks until they lost 25 per cent of their body weight. She implanted electrodes in the lateral hypothalamus, a region of the brain involved in feeding and energy balance. When the rats pressed a bar, nerve cells near the electrode were stimulated. Given a weak stimulation, animals don't bother working at the bar, but, given strong stimulation, they press it constantly.

Not unexpectedly, half of Fulton's rats were more sensitive to the stimulation reward when they were slimmed down than they were after they had been allowed to regain their normal weight.

In the other half, however, changes in body weight had no effect on brain stimulation reward. The researchers suspect that in this second group, the electrodes may have stimulated a nearby group of neurons associated with the rewarding effects of stimuli unrelated to food. According to a theory proposed by Shizgal, this effect is due to activation of nerve cells involved in the evaluation of goals and actions.

Fulton tested the hypothesis that the effect of weight loss on brain stimulation reward was due to lowered levels of leptin, and administered it into the rats' brains. In the first group, leptin mimicked the effect of excess body fat, and weakened the reward effect, making them less hungry. In most of the rats of the second group, however, leptin strengthened the reward effect, making them less inclined to eat.

This was a dramatic and unexpected result. Shizgal said that the leptin may be contributing to the regulation of energy balance by disposing these rats to spend more of their time engaged in activities unrelated to feeding.

Shizgal said that this was a difficult study, and credits Fulton for her persistence. "You are aiming electrodes at very small targets, and they don't always go exactly where you want. You really have to be determined to take something like this all the way through." Fulton got her BA from Concordia in 1996 and her MA in 1999, and is now continuing her studies at the CSBN.



Leptin group gray

Peter Shizgal, Stephanie Fulton and Barbara Woodside.

Magic words "weight loss" arouse media interest

Just mention the possibility of losing weight at this time of year, and you're bound to turn heads. Research on leptin done recently at the Centre for Studies in Beha-vioural Neurobiology is no exception.

A paper by graduate student Stephanie Fulton and Professors Barbara Woodside and Peter Shizgal on the modulation of brain reward circuitry by leptin will not only be published in Science, but will receive mention in the Canadian Medical Association Journal.

The researchers have been photographed and interviewed in the local media, and Woodside was delighted that her son considers her something of a star.

Professor Shizgal has done a phone interview with a writer for The Why Files, a science magazine on the Web. There have been queries from the Daily Telegraph, Britain's biggest newspaper, Newsday, CBC's Quirks and Quarks, and the Discovery Channel. The Dallas Morning News published an item on Monday.

Leptin is a hormone produced by the fat cells. The more fat there is in the body, the more leptin is released into the blood. Leptin is able to cross from the bloodstream into the brain, enabling the brain to obtain information about the body's energy stores, and affecting body processes. For example, female mammals become infertile when the level of body fat falls too low.

Tracing the brain circuitry and the neurochemicals involved in this process might provide new ways to combat obesity -- or to do many other things. While Fulton, Woodside and Shizgal are pleased with their week of fame, they are clearly uncomfortable with the idea that they might be feeding false hope for a "magic bullet" in the form of a leptin pill.

"We're not in the clinical domain at all," said Fulton firmly. "This is pure research, biology to teach us more about brain circuitry." However, Shizgal added, "providing these compounds are shown to be safe and effective, I see leptin and related pharmaceutical products as components of an integrative approach to combating obesity, along with a low-fat diet and exercise."

Copyright 2000 Concordia's Thursday Report.