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Insects and mammals share common fat-building pathway, study suggests

When it comes to gaining fat, insects and mammals may have something in common, researchers report in the Jan. 11, 2006, Cell Metabolism. The study finds that the so-called hedgehog (Hh) signaling pathway--an ancient suite of genes involved in determining the fates of many cell types--might also play an important role in fat formation in both flies and mice. The findings are the first to show a conserved effect of genes on fat storage from insects to mammals, according to the researchers.

The study results further suggest that the Hh pathway in mammals determines whether adult stem cells are fated for fat or bone. The findings suggest that drugs that target the Hh pathway might prove useful for the treatment of osteoporosis, diabetes, obesity, and lipodystrophy, a disease characterized by the absence of fat, said the researchers. The findings might also explain common traits normally associated with aging, they suggest.

"As we age, two striking things tend to happen almost across the board--our bones become thinner and we gain fat," said senior author, Jonathan Graff of the University of Texas Southwestern Medical Center. "Our findings are consistent with the idea that hedgehog signaling may diminish as we get older. Drugs that stimulate the pathway could possibly help to reverse or prevent this trend, building stronger bones while reducing fat."

The researchers found that flies in which the Hh pathway in the fat bodies was overactive gained less fat than normal. Conversely, treatments that blocked the action of the Hh pathway led to an increase in the insects' fat stores.

To see whether the same pattern might hold in mammals, the team then looked to the mouse. The animals' fat cells indeed expressed genes involved in the Hh pathway. In mouse cells, treatment with an Hh protein blocked the changes normally associated with the generation of fat, while methods that blocked Hh activity caused an increase in fat.

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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
10-Jan-2006


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