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.