Johns Hopkins School of Medicine scientists have shown for the first time that primitive fat cells must copy themselves at least twice before they can mature into full-fledged fat-storing cells. The finding, published online the week of Dec. 23, 2002, in the Proceedings of the National Academy of Sciences, may help provide new targets for understanding and treating obesity.

The finding also helps explain how the body makes sure that it can always store fat, a key to surviving when food is scarce (and an unfortunate ability when it is not). By requiring a primitive fat cell to copy itself at least twice before it matures and can't divide anymore, nature ensures a ready reservoir of the cells, the researchers say. While proliferation of these cells has long been recognized, this is the first evidence that those divisions are necessary for the cells' maturation.

"Fortunately or unfortunately, depending on how you look at it, food is not scarce in many parts of the world, and storing the excess calories can lead to obesity and many serious associated health problems," notes Daniel Lane, professor of biological chemistry at the school's Institute for Basic Biomedical Sciences. "Our finding may lead to new ways to tackle obesity, since we now know a crucial step in the body's ability to store additional fat, but that step would have to be targeted specifically."

Studying mouse primitive fat cells in the laboratory, the team discovered that the genes necessary for storing fat were turned on only after at least two cycles of cell division. Interfering with cell division at various points in the cycle prevented the cells from maturing, says Qi-Qun Tang, assistant professor of pediatric endocrinology and biological chemistry at Johns Hopkins.

When more calories are taken in than are burned, existing fat cells make and store more fat. But the body also recruits some primitive fat cells--preadipocytes --to mature, which increases the capacity to store fat in general, explains postdoctoral fellow Tamara Otto. If preadipocytes can't or don't mature, the scientists hypothesize, the body might not be able to store extra fat. What effects this might have on weight, appetite or health remain to be seen.

Importantly, Tad says, there seem to be biological differences between the cell divisions that allow preadipocytes to mature and those of other cell types, offering an opportunity to find a way to selectively prevent fat cells from forming.

Adds Lane, "We're very interested in finding markers that distinguish preadipocytes from full-fledged fat cells. We've found some, but they're in other types of cells, too. We're still looking for appropriate preadipocyte-only targets."

In a related paper, still in press, the researchers identify a gene responsible for making the cells divide, although there are likely others. This gene or its related protein could possibly be a target to prevent fat storage in animals, but much more work is necessary, the researchers add.

The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Authors on the paper are Tang, Otto and Lane.