Fat formation decoded

BOSTON, Dec. 31 (UPI) -- Two research groups have simultaneously discovered a critical gene responsible for fat cell development.

The gene encodes the PPARgamma protein and causes fat cell development, or aipogenesis. The discovery that fat cell development requires PPARgamma could offer a specific molecular target for weight-loss drug design.

"The most important implication of this research is that there is a single, unified pathway for the regulation of fat cell differentiation," Bruce Spiegelman, professor of cell biology at Harvard University in Cambridge, Mass., told United Press International. "It points out that the process requires PPAPgamma and, although other factors can promote aipogenesis, they probably do so by regulating PPARgamma. So this simplifies things. There's one major pathway controlling things."

Spiegelman's study and parallel research by Heidi Camp, a Pfizer Pharmaceuticals researcher, and colleagues at Sangamo Biosciences in Richmond, Calif. are reported in the January 1 issue of Genes & Development.

Adipogenesis is a process in which a mesenchymal cell differentiates into a pre-adipocyte cell, which then becomes a lipid-filled, or fat-filled, adipocyte cell. The research groups discovered that PPARgamma is responsible for the transition from pre-adipocyte to fat cell.

Spiegelman and colleagues created cells lacking PPARgamma. They found that without PPARgamma, adipogenesis would not occur. This evidence suggested that PPARgamma is the critical player in the fat differentiation pathway.

"This study provides further proof that PPARgamma is required for the development of fat cells," Dr. Bradford Lowell, associate professor of medicine at Harvard Medical School in Boston, Mass., told UPI. "The biology of fat cells is a very important area of study since obesity is responsible for a large amount of morbidity and mortality."

Camp and her colleagues took Spiegelman's discovery one step further and identified the

specific form of PPARgamma responsible for fat cell development. She found that PPARgamma gene encodes two different protein products called "isoforms," gamma1 and gamma2. She generated two cell populations, one lacking PPARgamma2 and another lacking both isoforms. As in Spiegelman's research, both cell populations failed to differentiate into fat cells. Camp then expressed PPARgamma1 or PPARgamma2 into the cells lacking both isoforms. She found that PPARgamma2 alone induces adipogenesis.

"If you want to try and manipulate fat formation, it makes the process clearer," said Speigelman. "It's now conceivable that such manipulation could happen."

(Reported by Bruce Sylvester from West Palm Beach, Fla.)