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Thursday, December 17, 1998 Published at 14:54 GMT


Scientists make thin mouse

Obesity is a major health problem in the West

Scientists have genetically altered a mouse to make it thin. It is predisposed to eat less, lose weight and have a higher metabolic rate. Its body weight is just three-quarters that of a normal mouse.

Although animals that are designed to be obese have already been produced in the lab, this is thought to be a first in the on-going research to discover what controls eating behaviour. In particular, scientists want to understand how the body tells itself it is hungry or full-up.

The thin mouse sheds new light on this messaging system and could eventually lead to novel drugs to treat obesity in humans - one of the major health problems now facing Western societies.

Brain chemical

Scientists at the Elliot P. Johnson Research Laboratory in Massachuesetts, USA, bred a number of animals that lacked the gene which codes for a substance called melanin-concentrating hormone (MCH). This is a brain chemical that is known to promote the desire to eat.

The reduction in body weight of these mice was evident from about five weeks after birth. By the time they were 17 weeks old, the male mice which could not produce MCH weighed 28% less than the normal mice. The weight difference between the female altered animals and the normal rodents was only marginally less pronounced.

In all respects, the thin mice were healthy and just as active as wild mice. The major difference was that they ate less and appeared to burn-up their food intake more rapidly. The Joslin team also noted that when deprived of food, the thin mice did not react to their starvation by slowing down their metabolism and trying to eat more - as would be expected. Instead, they continued to eat less and lost even more weight.

Appetite control

Dr Eleftheria Maratos-Flier, who led the research, said it was surprising that merely knocking out the MCH gene could control the appetites of the mice, especially since there are several other neuropeptides that promote eating.

"It was not thought it would be one pathway that would have such a significant effect. It was thought that the appetite would be regulated by multiple factors and multiple pathways."

She said it was also remarkable given that the weight loss also led to low levels of leptin. This molecule has created huge excitement in recent years because of its apparent importance in regulating eating behaviour. Mice that have no leptin become obese, leading to the idea that raising levels of the molecule could be used as an aid to dieting.

But Dr Maratos-Flier said some obese people already have high leptin levels and her research suggested controlling MCH might now be a more fruitful line of research.

"Any approach that directs itself more at the neuropeptides mediating eating is probably going to reveal more direct targets [for new drugs] that are more widely applicable."

The research is published in the science journal Nature.

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Dr Eleftheria Maratos-Flier

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