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Fat Flies and Rotund Rodents

As anyone on a new year's diet can attest, gaining weight is much easier than burning it off. Humans aren't the only ones capable of packing on the pounds, however. New research indicates that insects store fat in one of the same ways mammals do. Identifying the fat management pathways insects and mammals have in common may eventually help scientists develop new ways to fight obesity, say the researchers.

Fat cells form when a unique class of stem cells make a critical decision: They either become osteoblasts, which develop into bone cells, or preadipocytes, which give rise to fat cells. Exactly which messages tell a stem cell to become a fat cell rather than a bone cell remain a mystery, however.

To learn more about the process, Jonathan Graff, a molecular biologist at the University of Texas Southwestern Medical Center in Dallas, studied a set of genes known to impact development in humans, flies, and many other animals. To see if the set, called the Hedgehog suite, also influences the development of fat cells, Graff and his research team bred mutant flies missing select Hedgehog genes. Flies without the genes were fatter, survived starvation better, and had higher overall levels of lipid and fat related proteins than did flies with an intact gene suite, the team reports this month in Cell Metabolism.

The Hedgehog genes appear to play a similar role in mice. When the researchers exposed mouse stem cells to drugs that prevent some of these genes from working, the cells gave rise to fat cells. When, on the other hand, the team expressed the Hedgehog genes at higher than normal levels in these stem cells, the cells became bone cells instead. Graff says this discovery might help explain why people tend to gain weight while losing bone mass as they age. These results are the first indication that Hedgehog genes regulate fat and bone cell formation, he says, and the first example of an insect and a mammal having the same fat regulatory pathways.

The findings are intriguing, says Barbara Kahn, a professor of medicine at Harvard Medical School, but they only scratch the surface of the complex cellular message systems that regulate fat cell formation in mammals. "It's possible the Hedgehog pathway might one day be harnessed for drug treatments that target osteoporosis and obesity," she says, "but to really be clear about its role in physiology, one would need to do more research."

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