Skinny mice defy obesity

Lean mouse: Hope for the clinically obese

By BBC News Online's Matt McGrath

Genetically engineered mice which never put on weight could hold the key to a fat-free future for humans, say scientists.

Researchers at Smith Kline Beecham and the Dunn Human Nutrition Unit in Cambridge, UK, have developed mice that eat far more than normal but remain leaner and lighter.

What these mice have told us, in fact, is that this is a viable drug target to treat obesity.

Dr John Clapham

The lab rodents over-produce a human protein which ensures food is turned into heat, rather than stored as fat.

Reporting in the journal Nature, Dr John Clapham and colleagues say their mice make large amounts of Uncoupling Protein 3 (UCP-3) in the mitochondria of their muscle cells.

Mitochondria are often described as the tiny internal combustion engines of cells. They unlock the energy contained in food to make a chemical fuel called adenosine triphosphate (ATP).

But extra UCP-3 causes the mice to burn off energy without making ATP - their bodies produce more heat instead. This process makes the metabolic rate of the transgenic mice step up a gear. As a result, they are able to eat large amounts of food yet weigh less than normal mice.

Diet and exercise

Speaking to BBC News, Dr Clapham compared the process in mice to revving up a car engine.

Dr John Clapham: New therapies could aid weight loss

"If you slip the clutch on the car, you are still using up fuel, but no matter how hard you rev the engine that car isn't going to move and all that fuel is expended as heat".

Dr Clapham and his team write in their journal paper that even though the transgenic mice ate 15-54% more food than normal mice, their fat-tissue mass was 44-57% less.

The success of the work gives scientists hope that they will be able to develop a therapy for humans.

"What these mice have told us, in fact, is that this is a viable drug target to treat obesity," Dr Clapham said. However, he stressed that diet and exercise should remain the first courses of action.

New generation of drugs

He said 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.

The mice eat as much as they like but stay thin

And he said new drugs would work differently to the current generation of appetite suppressers.

"If you over-eat or under-exercise, you will put on weight. Appetite suppressers, of course, reduce appetite but new drugs based on our research would act on the other side of that equation.

"They would increase energy expenditure and they would increase metabolic rate, which could be very important."

Professor Nick Finer, director of the Centre for Obesity Research, Luton and Dunstable Hospital in Luton, UK, welcomed the new study.

"We know from food surveys and large studies that part of the problem with obesity is our low level of energy expenditure and activity.

"This research shows us is it is possible to treat obesity by increasing energy expenditure, in this case in mice but it might also be possible in people as well."