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Brain Peptide Foreshadows Safe Slimming Pill
by John Newell
Former Science Editor, BBC World Service

British scientists at the Royal Postgraduate Medical School in London and at Cambridge University's Department of Anatomy, led by Professor Stephen Bloom, have discovered how our appetite for food is controlled in the brain. They believe their research could lead to a safe way to control appetite and weight.

Professor Bloom and his colleagues have shown that a peptide known as Glucagon-like peptide 1, or GLP 1, powerfully inhibits feeding in rats which have been deprived of food. But when an antagonist to the brain receptor for GLP 1 is also administered to the rats, the inhibition is lost. Professor Bloom believes that, after further research, a synthetic version of GLP 1 could become "an effective and safe treatment for obesity."

GLP 1 was first discovered by Professor Bloom about eight years ago, since then it has become clear that it is highly conserved is found in exactly the same form) in every mammalian species studied.

This suggests that, like other very highly conserved peptides and proteins, GLP 1 performs a vital and irreplaceable function. But that function has only recently been discovered, through work reported in "Nature" Magazine (4 January 1996.)

In the experiments GLP 1 was injected, under anaesthetic, into the cerebral ventricles of the brains of rats which had been deprived of food for long enough to make them extremely hungry under normal conditions. The effect of GLP 1 was to reduce the intake of food when offered by 95%, compared to the intake of untreated rats that had been deprived of food in the same way. In further experiments, a specific antagonist to receptors for GLP 1, exendin, injected into the cerebral ventricles of rats which had earlier been injected with GLP 1, was found to restore their appetite.

This implies that GLP 1- is normally produced when enough food has been consumed, and normally acts as a chemical signal to the brain, "telling" it that the appetite for food has been satisfied. GLP 1 administered from outside has the same effect. It is clearly a very powerful and overriding messenger as it is completely effective even when rats are starving.

Clinching Proof
Further evidence that GLP 1 is the vital chemical messenger is provided by the effect of exendin. The molecule of this peptide competes effectively with molecules of GLP 1 for receptors in the brain, and so selectively blocks the effects of GLP 1 - and of nothing else.

The fact that exendin restores appetite in rats previously given GLP 1 is clinching proof of the role of GLP 1 in controlling appetite at the level of the brain.

Exendin, however, only stimulates appetite in rats which are full of food. If it is given to rats which have been deprived of food, it has little or no effect.

This apparently paradoxical effect in fact shows that GLP 1 has no function in a hungry animal, or human. This peptide hormone is only functional when an animal has had enough to eat. At that point, and at that point only, blocking the effect of GLP 1 makes an animal, and by implication a human, feel hungry.

This suggests that many overweight people, rather than simply being greedy, may be suffering from a defect in the supply of GLP 1 in their brains, Such people often do not feel full even when they have had a lot to eat, and may have to eat excessively in order to feel satisfied. A defective supply of GLP 1 would explain such symptoms.

In the future Professor Bloom believes, a synthetic version of GLP 1 taken as a pill might compensate for the deficiency and make it easy for those affected not to overeat.

Excess Weight
This is an exciting time for research into the control of appetite. About a year ago researchers discovered a gene which makes mice, and by implication humans possessing it, gain excess weight. Professor Bloom believes that this gene's protein product may in turn control the production of GLP 1 in the brain.

A team of researchers at the University of Liverpool has also identified a molecule that is important in appetite control, known as Neuropeptide Y or NPY. This induces the sensation of hunger in the brain.

The Liverpool scientists believe it may be possible to control appetite by using a nasal spray containing a drug that counters the effects of NPY. Intensive research is now exploring the relationships between GLP 1, NPY and the obese gene. It is likely that they will soon lead to effective and safe means of appetite control for those who, for reasons beyond their control find normal methods of weight control very difficult or impossible.

However doctors stress that many people overeat for psychological rather than physiological reasons, and that for such people it is important to find and treat the real cause of their disorder.

For more information contact:
Professor Stephen Bloom
Endocrine Unit, Royal Postgraduate Medical School, Hammersmith Hospital
Du Cane Road, London W12 ONN. Tel: +44 181 743 2030

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