The fat track: signals between cells keep creatures lean.

Fat is a fact of life for creatures great and small, but researchers know little about why some stem cells transform into fat cells rather than, for example, muscle or bone. Now, a team of researchers has found a clue: A series of signals between cells that is common to insects and mammals appears to influence fat formation.

The finding could offer new avenues for research into treating conditions such as osteoporosis and obesity. It also supports biologists' use of the simple fruit fly as a model for mammals in fat research.

Stem cells develop into different types of cells with the guidance of signals from, for example, hormones or nutrients sent by other types of cells. One such series of signals, known as the hedgehog signaling pathway, occurs in a variety of creatures, from insects to people. Hedgehog signaling plays an important role in determining the form that cells take as they mature and also sets patterns for the structure of tissues and organs.

To see how hedgehog and other signaling pathways might affect fat development, endocrinologist Jonathan Graff of the University of Texas Southwestern Medical Center in Dallas and his colleagues studied the effects of activating and blocking the hedgehog and other pathways.

In both fruit flies and mice, activating the hedgehog pathway resulted in low-fat animals. Blocking the signals stimulated fat cell development, the team reports in the January Cell Metabolism. Since the pathway controls a cell's potential fate, active hedgehog signaling may reduce fat formation by designating a cell as bone, for example, rather than fat, Graff says.

The simplicity of the relationship suggests that it might be possible to manipulate hedgehog signaling with drugs and thus treat conditions such as obesity, diabetes, and osteoporosis, Graft says. "From the beginning, these studies were thought of as a potential way to alleviate an enormous crisis we're facing. The health implications are enormous," he adds.

The study results also suggest that findings on fat formation in fruit flies could be applied to people. "It's this common connection between insects and mammals that's provocative," Graff says.

"It's an important paper," says endocrinologist Evan Rosen of Beth Israel Deaconess Medical Center in Boston. But he says he's uncertain whether hedgehog signaling will ever provide an avenue for treatment. If it does, it won't be soon, Rosen warns.

The hedgehog pathway contributes to the development of some cancers, he notes, so researchers would need to isolate the effect of hedgehog signaling on fat cells. If a treatment reduced fat cell development but increased cancer risk, "most people wouldn't make that trade," he says in the same issue of Cell Metabolism.

Even for obesity, Rosen adds, "blocking fat cell formation is a very bad way to treat [the problem]." He says that excess fat can best be prevented by balancing calorie intake and energy expenditure--also known as dieting and exercising.