Weight Is a Prickly Problem: Key Role Found for Hedgehog Signaling in Controlling Fat Storage

When they look to hedgehogs for help in controlling weight, the war has been lost.

"Obesity is a widespread condition in humans and has many serious consequences. Not only are overweight people faced with surcharges on airplanes but they also have a much higher risk of contracting a number of potentially fatal diseases. A considerable amount of research effort is currently focussed on the problem of weight control but to date genetic screens for factors that cause obesity have been hampered by the lack of an appropriate system.

Putting it bluntly, yeast do not become overweight. However, fortunately (for us) flies do and this has provided scientists in Josef Penninger's group at the IMBA (Institute of Molecular Biotechnology) in Vienna with a unique handle on the process. Their initial and highly surprising results are reported in the present issue of Cell...

Application of the screen resulted in a total of about five hundred genes that seemed somehow to be involved in fat metabolism. Many of these had been previously implicated in the process, which confirmed that the method yielded plausible results. Some of the genes identified were found to be active in neurons, suggesting strongly that fat storage in flies can be regulated by neuronal genes: it is clearly the case in mammals that feeding behaviour is under the control of neuronal genes. And some of the candidate regulatory genes worked in muscles: this too is similar to the situation in mammals...

But perhaps the most significant result of the work was the finding that genes associated with the so-called "hedgehog" signalling pathway are involved in the regulation of fat storage. Hedgehog is one of the "pattern" genes in the fly, responsible for ensuring that developing cells assume the correct identity.

The idea that hedgehog also plays a part in controlling fat levels in flies was extremely interesting as it was consistent with previous findings that inhibition of hedgehog signalling protects mice from gaining weight...

Taken together, these results confirm a role in mice -- and thus presumably in man -- for hedgehog signalling in the production of white but not brown adipocytes...

The finding that the hedgehog signalling pathway inhibits the formation of white adipose tissue while leaving brown adipose tissue intact is of enormous potential therapeutic importance.

No, it's not.