Researchers have pinpointed a protein that seems to open a metabolic waste valve, allowing the body to burn off fuel as heat rather than storing it for later use. The protein, described in the current issue of Nature Genetics, apparently allows cells to bypass a crucial step in the pathway that converts sugar and fat molecules into the cell's energy-storing currency, ATP. Instead, the chemical energy of the food seems to go straight into heat. Besides helping researchers understand the mechanisms that control body temperature and metabolism, the finding could also point the way to drugs that might open the waste valve a little wider, slimming down obese people.
The protein, identified by a team of researchers led by geneticist Craig Warden at the University of California, Davis, is a more widespread version of one found in the heat-generating tissue known as brown fat. The brown-fat protein--called uncoupling protein 1 (UCP1)--is known to work in the cell's power plants, called mitochondria, which break down sugar and fat molecules to create a gradient of positive charges, or protons, across their membranes. The mitochondria ordinarily harness the proton gradient to make ATP. But high levels of UCP1, explains Warden, allow the protons to seep through the membrane and generate nothing but heat.
By searching genetic databases, Warden found a similar protein, UCP2, that is produced in a wider range of tissues, including skeletal muscle, lung, heart, and kidney--suggesting that it might have a larger influence on overall heat regulation than UCP1. The researchers don't have direct proof that UCP2 works in the same way, but when Warden's colleagues at the National Center for Scientific Research in Meudon, France, expressed the protein in yeast cells, they found that the proton gradient decreased. In addition, yeast with high levels of UCP2 grew very slowly, suggesting that they were dissipating much of their food energy as heat rather than converting it into energy for growth.
The finding "provides a whole new approach to both understanding and manipulating energy expenditure," says endocrinologist Jeffrey Flier of the Beth Israel Deaconess Medical Center in Boston. At first glance, the new protein also looks like just the thing to keep calorie-laden meals from ending up as unwanted pounds. While several companies have found drugs that manipulate UCP1 levels in animals, they had so far not proved useful in humans. But because UCP2 "is definitely there in tissues like muscle and fat," says Flier, "the likelihood that one might be able to manipulate it seems greater."