Skinny mice defy obesity

GENETICALLY ENGINEERED mice which never put on weight could hold the key to a fat-free future for humans, according to research work being carried out by SmithKline Beecham and Cambridge University, eastern England.

The collaboration has developed mice that eat far more than their normal cousins but remain leaner and lighter. The laboratory's rodents over-produce a human protein that ensures food is turned into heat rather than stored as fat. Dr. John Clapham from SmithKline Beecham's research centre in Harlow, southern England, and who is leading the research said that the mice make large amounts of an uncoupling protein 3 (UCP-3) in the mitochondria of their muscle cells.

Often described as the tiny internal combustion system of the cell, mitochondria unlocks the energy contained in food to make a chemical fuel called adenosine triphosphate (ATP). But extra UCP- 3 causes the mice to burn off the energy without making ATP and their bodies produce more heat instead. This process makes the metabolic rate of the transgenic mice step up a gear. The result is they are able to eat large amounts of food yet weigh less than normal mice.

Although the mice ate 15 to 54 per cent more food than their normal colleagues, their fat-tissue mass was 44 to 55 per cent less. ``What the experiments show us is that this is a viable method of treating obesity. But diet and exercise must remain the first course of action,'' said Dr. Clapham.

Any new therapy should be used to aid the degree of weight loss achieved on a diet and crucially help the maintenance of that loss over time. He predicted new drugs of the future would work differently to the present generation of appetite suppressers.

``If you over-eat or under-exercise you will put on weight,'' said Dr. Clapham. ``Appetite suppressers, of course, reduce appetite but new drugs based on our research could act on the other side of that equation. They would increase energy expenditure and increase metabolic rate that could be very important.

Reporting their findings in the journal Nature, the scientists said there was previously some doubt over the role of UCP-3 in the regulation of energy expenditure in humans. The data was unclear but ``despite increased energy intake, over-expression of UCP-3 elicits a marked reduction in body weight, a marked reduction in adiposity (fat), and improved insulin sensitivity.''

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