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Skinny worms provide new approach for obesity drugs

By Colin Ricketts - 24 Mar 2011 14:31:0 GMT
Skinny worms provide new approach for obesity drugs

Scientists at the University of California, San Francisco have found a new way to understand human obesity in the unlikeliest of animals - the traditionally long and thin worm.

The team, who publish their research in the journal Nature Chemical Biology this month, found that a small group of chemicals in worms is responsible for regulating fat storage.

Using microscopic worms called C elegans; the researchers tested a variety of chemical compounds and found they could control their weight with no change in diet or their normal worm lives.

If their results can be transferred to humans, then a new generation of drug treatments for obesity and related diseases like diabetes and some cancers could be on the way. It will also show that worms can provide a productive testing ground for human medical treatments.

The UCSF team knew that worms use fat in the same way that we do - to store energy and build tissue - and regulate fat with similar genetic mechanisms.

They took 3,200 chemical mixes and tested them on 3,200 groups of C elegans worms, dying fat molecules red so they could spot the most coloured and thus fattest worms easily. They finally narrowed down their selection of chemicals to around 10 which have an effect on the metabolism and fat storage; results which were repeated with cultured cells from other species.

The target for their treatments was a molecular complex called AMP-activated kinase, which senses the availability of cellular energy and which both worms and humans have.

''The compound that we get from our worm screen can act on this kinase complex as well if not better than anything else that is out there,'' said Kaveh Ashrafi, PhD, an associate professor in the UCSF Department of Physiology.

But the real breakthrough, Ashrafi believes, may be in discovering that worms are a fertile testing ground.

''A lot of the drugs that are in clinical use or development today were discovered basically by chance,'' he said. ''If we understood everything about everything, we could probably design the right compounds. But the reality is our understanding of many of the biological principles and chemical principles are still in their infancy.''