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Hunger hormone discovery boosts fight against obesity

Health Editor,Jeremy Laurance
Friday 11 November 2005 01:00 GMT
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The discovery of a new hormone that suppresses appetite has been hailed by scientists who said it opened a new front in the search for a treatment for obesity.

The hormone, obestatin, is a sibling to ghrelin, which increases appetite, leading researchers to call them the "duelling hunger hormones".

The finding surprised scientists, who believed all the key hormones involved in appetite control had been identified. But the discovery of obestatin could explain why treatments based on existing hormones have failed.

Researchers at Stanford University School of Medicine who injected rats with a synthetic version of obestatin found they ate half as much as rats given no injection. The treatment also slowed the movement of digested food from the stomach to the intestine.

Commenting on the finding, published in Science, Greg Barsh, professor of genetics at Stanford University, said: "There are several known pathways that regulate body weight. This work is notable because it represents a completely new pathway."

The search for treatments for the global epidemic of obesity has engaged thousands of scientists around the world for decades. But despite frequent claims of success, progress has been slow.

Ghrelin was discovered in 1999 and for years scientists hoped it would yield a treatment that would help weight control. It followed the discovery of leptin in 1994. Leptin was seen at the time as the Holy Grail that would yield the key to the control of obesity.

Both hormones, while playing key roles in appetite regulation, failed to act as expected when used as treatments. Scientists hope the new finding may clear up confusion about how the appetite-regulation hormones work.

As the ghrelin protein stimulates appetite, scientists expected experiments in animals in which the gene for ghrelin was switched off would depress appetite. In fact, switching off the gene had almost no effect.

The discovery of obestatin offers an explanation. Deleting the gene for ghrelin also takes out obestatin. So the rats lost their appetite-stimulating and appetite-suppressing hormones at the same time.

Aaron Hsueh, an endocrinologist and professor of obstetrics and gynaecology at Stanford, who led the study, said it was rare for more than one hormone to come from a single gene sequence. Even more unusual was for two hormones from the same gene to have such opposite effects. Obestatin behaves in some ways as "anti-ghrelin".

"That was the big surprise," said Professor Hsueh. "A better understanding of the roles of ghrelin and obestatin in the intricate balance of energy homoeostasis and body weight control may be essential for successful treatment of obesity," the authors write. The need is urgent. Waistlines are expanding so fast that within 10 to 15 years it is predicted that obesity could overtake smoking as the UK's biggest killer. There are 24 million adults who are classed as overweight.

The cause of the growth is an imbalance between the calories people consume and the energy they expend.

Although we are eating 750 fewer calories a day on average than 20 years ago, activity levels have fallen by 800 calories. Out of this small imbalance has come the wave of obesity. Numbers of obese people have trebled since the 1980s, with 22 per cent of men and 23 per cent of women now classed as obese.

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