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Drs. Yu-Hua Tseng, and Atul J. Butte of Children's Hospital Boston and HMS, shared first authorship on the study, which appears in the June edition of the journal Nature Cell Biology.

In laboratory studies of mouse cells, the research team identified genes that govern how precursor cells give rise to mature brown fat cells. There are two main types of fat cells in the body -- white and brown. White fat cells are the ''conventional'' form of fat that we all recognize. They are designed to store energy for use in times of need. Chocked full of lipid droplets, these big cells accumulate under the skin and around internal organs.

By contrast, the main role of brown fat cells is to burn energy and generate heat. They contain small lipid droplets tucked between tiny energy factories called mitochondria. In mice, brown fat cells are found throughout the body and are present during the entire life cycle. In humans, they are principally found in the neck area of newborns, helping their tiny bodies generate heat. Brown fat cells largely disappear by adulthood, but their precursors still remain in the body, lodged in white-fat depots.

The researchers compared cell lines from normal ''wild-type'' mice to cell lines from mice that genetically lacked key components of the insulin-signaling network which are important to insulin's role in letting food nutrients enter the body's cells. If cells resist insulin, the body cannot get the energy it needs. This ''insulin resistance'' is the main culprit in the onset of in type 2 diabetes. Being overweight or obese has long been implicated with insulin resistance and type 2 diabetes and also raises the risk for heart disease, stroke and cancer.

The team studied ''knockout'' cell lines of brown preadipocytes that lacked insulin receptor substrates (IRS) numbered 1 through 4, which are the first steps in insulin signaling inside the cell. In cell lines lacking IRS1, the precursors failed to develop into mature brown fat cells. Importantly, when they added the gene for IRS1 back into the knockout cells, the precursors recovered most of their ability to differentiate into brown fat cells. Varying effects occurred with the knockout of genes for IRS2, IRS3 and IRS4. Using DNA chips to analyze these cells, a strong genetic pattern emerged that predicted the potential of precursors to differentiate into mature brown fat cells.