Gene variations police the storage of fat

With high-calorie foods at every turn, obesity is rampant in the Western world. Some people, however, just don’t seem to get fat even if they try to put on pounds.

Researchers may have found out why. They’ve uncovered genetic variations controlling a calorie-draining spigot in the body. The variations modulate production of a molecule called uncoupling protein 2 (UCP2), which converts calories into heat instead of fat.

Four years ago, scientists identified the gene that encodes UCP2 (SN: 4/8/97, p. 142). Since then, researchers have been looking for variations in the gene to help explain obesity, says geneticist Eric Ravussin of Louisiana State University in Baton Rouge. He’s worked extensively on the genetics of the Pima Indians of Arizona, who have some of the highest rates of obesity in the world (SN: 8/12/95, p. 103).

A group of researchers from several Austrian and French institutes report in the June Nature Genetics that variations in the so-called promoter–a control region–near the gene for UCP2 seem to influence risk of obesity. Wolfgang Patsch of the Landeskliniken Salzburg, an Austrian research hospital, and his colleagues studied the gene variations in laboratory-grown cells and in populations of obese or svelte Austrians. In both the cells and the people, the activity of the UCP2 gene in fat cells was higher in the presence of one variation than of the other. What’s more, the researchers found that the risk of obesity was modestly but measurably lower for the people in the study who showed the higher gene activity.

Energy banked inside cells is akin to water stored behind a hydroelectric dam, says Mary-Ellen Harper of the University of Ottawa. The protein UCP2 acts like a leak in the dam. Any genetic variation that increases the amount of UCP2 also increases energy leakage, so less energy is stored as fat.

The authors note that a 1 percent increase in energy-storage efficiency for a person translates into 1 kilogram of fat accumulated per year. “It doesn’t take much over time to make a significant difference,” says Harper.

More than half the volunteers examined in the study had the form of the gene promoter associated with high fat storage. Patsch’s team calculates that without this common variant of the promoter, there would have been 15 percent fewer cases of obesity among the study subjects.

Ravussin judges this estimate to be a little high. He notes that many genes underlie obesity and it’s not yet clear how much of a role this promoter plays.

The observation that the variant of the UCP2 promoter that stores more fat is the standard among the Austrians in the study reflects that country’s history, says Patsch. “I think at certain times it was an advantage to hang on to your energy,” as during a famine, he says. Now, with high-fat foods readily available, this storage mechanism is a disadvantage, he notes.

The team is now studying the effects of variations in the UCP2 promoter in other parts of the world, Patsch says.