Like most things in the body, metabolism is governed by a complex interaction among genes. In particular, a family of proteins called PPARs (for peroxisome proliferator-activator receptors) controls how the body uses sugar and fat. One member of this family, PPAR-gamma, acts as a master switch that drives the formation of fat cells and regulates the storage of fat. The receptor snatches fat from the blood and squirrels it away inside fat cells. By whisking fat from the blood, PPAR-gamma encourages muscle to burn sugar and allows the body to remain sensitive to insulin. Drugs that activate PPAR-gamma are currently used to treat diabetes. Although they don't help people lose weight, the drugs do restore patients' sensitivity to insulin.
A sister protein, called PPAR-delta, regulates how muscles burn fat. When kept on a high-fat diet, mice that lack PPAR-delta become obese. Mice that are engineered to produce an overactive version of the receptor in their muscle tissue remain sleek and lean. PPAR-delta revs up cellular fat-burning pathways and beefs up the animals' slow-twitch muscle mass. This type of muscle, highly developed in marathon runners and migrating birds, prefers to use fat as an energy source. The engineered animals put this muscle to good use. When placed on a rodent-sized treadmill, these "marathon mice" will run twice as far as their normal relatives.