New drug could encourage couch potatoes to get moving

By Daniel Martin for the Daily Mail
Updated: 01:58 EST, 4 June 2009

A new drug that could give hope to couch potatoes by encouraging them to go to the gym is being developed by scientists.

Tests on mice have shown that switching on an appetite-regulating hormone in the brain makes them engage in twice the amount of physical activity.

Although a similar drug for humans could be many years away, researchers believe it offers useful avenue for future research.

Around a quarter of British adults are obese, and experts believe that more than half will be by 2050 - unless people change their diets or take more exercise.

Failure to do so will cause a massive increase in the numbers with heart disease, stroke, type two diabetes and certain forms of cancer, putting the NHS at risk of bankruptcy.

Now, scientists at the Harvard Medical School in Massachusetts, are working on a pill which they hope could diffuse the obesity timebomb by encouraging obese people to get moving.

Endocrinologist Dr Christian Bjorbaek said: 'This gives us the opportunity to search for drugs that might induce the desire or will to voluntarily exercise.'

The mice became morbidly obese and severely diabetic, as well as very sluggish, after being bred to lack the appetite-regulating hormone leptin or the ability to respond to it.

But blood sugar control in the animals - something which is affected by diabetes - was completely restored by returning leptin sensitivity to a single class of brain cells known as POMC (pro-opiomelanocortin) neurons.  

Dr Bjorbaek, whose findings are published in Cell Metabolism, said: 'Just the receptors in this little group of neurons are sufficient to do the job.' 

The animals spontaneously increased their exercise levels despite the fact that they remained profoundly obese. They also began eating about 30 percent fewer calories and lost a modest amount of weight.

Remarkably, their blood sugar levels returned to normal independently of any change in their eating habits or weight. The animals also doubled their activity.

Whether this particular bunch of neurons also plays a similarly important role in animals that are lean remains uncertain.

Dr Bjorbaek added: 'It may be that in the context of severe obesity and diabetes, these neurons do something they don't normally do.' But, even if that were the case, it may not matter when it comes to its potential as a therapeutic target, he said.

Leptin was first identified 15 years ago and made famous for its ability to curb appetite and lead to weight loss.

It is known to play a pivotal role in energy balance through its effects on the central nervous system, specifically by acting on an area of the brain called the arcuate nucleus (ARC).

The ARC contains two types of leptin-responsive neurons, the POMC neurons, which cause a loss of appetite, and the AgRP (Agouti-related peptide) neurons which do the opposite.

Studies had also revealed a role for leptin in blood sugar control and activity level, also via effects on the ARC. But scientists still didn't know which neurons were responsible, until now.