Increasing the activity of a protein in mice mimicked the effect of exercise
by Tamara Traubman
British scientists have created a strain of mice that gobble up much more food than average without getting fat. Obesity experts, who read the study ahead of its publication today in the scientific journal Nature, said its results seemed almost too good to be true. Unlike most drugs under development, which suppress the appetite, the treatment actually made the mice eat much more than their normal friends, but even though they were no more active - they remained much thinner.
The researchers, Dr. John Clapham and his colleagues from the British pharmaceutical company "SmithKline Beecham", added to the mice a gene responsible for the production of a protein called UCP-3 in humans and caused the mice to produce it in extremely large quantities. The increased production of the protein, which is mainly active in the muscles, caused the bodies of The mice react as if they performed physical activity and burn more energy.
The transgenic mice consumed 15-28% more calories than the normal mice, but remained leaner than them. To encourage them to eat more, Clapham added corn oil to the food, which makes the food a delicacy for them. As a result, the transgenic mice ate 33-54% more than their peers, but their fat mass decreased by 44-57%.
Dr. Clapham said in an interview yesterday that it is still not clear to him why the mice became gluttons. "My guess is that their energy burning rate was increased as a result of the overactivity of the protein, so they had to eat more to adapt to the greater energy expenditure."
If a similar drug is developed to treat humans, it will have a huge market: the Western lifestyle, which combines little physical activity and eating regardless of the body's needs, has meant that there are about 200 million obese people living in the world today. Although it is clear to everyone that people get fat because they eat more calories than they burn, the mechanisms that control the process are still largely unknown. "It is clear that there is a pathway related to the regulation of body weight, which was not known until now. This shows how much knowledge we still lack in understanding the biochemical pathways of obesity," said Clapham.
Prof. Elliot Barry from the Department of Human Nutrition and Metabolism at the School of Medicine of the Hebrew and Hadassah University, says that "it is possible that in the long run, the slimming effect of the protein will be canceled because another mechanism will perform the role of the defective mechanism".
Several scientists said that protein therapy in humans may prove problematic, because instead of adopting proper eating habits, the patients will eat more and have to take the drug for the rest of their lives. "In my opinion, that won't be the problem," said Clapham, "the important thing is that when fatties lose weight, their metabolic rate also decreases and therefore they feel a huge urge to eat. The method can actually raise the metabolic rate back to normal. In any case, they will have to to go on a diet, because the protein does not slim down, but prevents obesity."
Clapham warned that "the research is just beginning." This, after a hormone called leptin was discovered six years ago. Its effect on mice was amazing: they lost their appetite and became thin in a short time. But a study last year that tested how it works in humans showed that it is not the long-awaited miracle drug - the participants lost little, if any, weight.
{Appeared in Haaretz newspaper, 27/7/2000}
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