Science : A dream drug for weight watchers?

 作者:羊舌阙     |      日期:2019-02-27 10:19:03
By Michael Day THE race for a perfect slimming pill has taken a fresh turn after American and French researchers discovered a protein that they believe governs the rate at which the body burns off fat. The findings are strikingly different from other recent research on obesity, which has focused on the hormones that regulate appetite. For years, biologists have been trying to work out how cells regulate the rate at which energy is burnt off or stored as fat. It is clear that a protein called uncoupling protein 1 (UCP1) causes mitochondria, the powerhouses of cells, to burn energy off as heat instead of using it to power chemical reactions in the body. But UCP1 cannot be an important regulator, because it is found only in brown fat, and adults have almost no brown fat. Now Craig Warden at the University of California, Davis, and his colleagues in France and North Carolina, have found a second protein that they believe does the same job in mitochrondria as UCP1. The crucial difference is that the protein, which they have called UCP2, is found in many adult tissues, particularly in skeletal muscle and ordinary body fat. “This molecule has a unique role in regulating weight and body temperature,” says Warden. The team compared the effects of a high-fat diet on two groups of mice—one group that was naturally prone to obesity and another that was naturally thin and resistant to obesity. The researchers measured the levels of UCP2 in both groups. In the obesity-resistant mice, UCP2 levels rose sharply in response to the diet. By contrast, in obesity-prone mice, levels of the protein hardly rose at all. Warden speculates that, as the level of this protein increases, fat is burned off (Nature Genetics, vol 15, p 269). Warden has also begun studies in people. He has already found that UCP2 levels rise in their bodies in response dietary changes. Although it is too soon to draw firm conclusions, Warden speculates that people who are naturally lean have more of the protein in their bodies than people who are overweight. The team has mapped the gene encoding the protein to regions of chromosome 11 in humans and chromosome 7 in mice. These regions have already been linked with diabetes and obesity. Theoretically, it might be possible to give UCP2 to people with naturally low levels of the protein as a drug to help weight loss. But Warden says it will be a long time before this is possible. And, he warns, it might not help very obese people because, he argues, it might mean raising body temperatures to fever levels. Bradford Lowell of Harvard Medical School in Boston, who is also studying the role of uncoupling proteins in metabolism, says the findings are “a major breakthrough towards understanding the molecular basis of energy expenditure”. He believes the work may help to explain what causes obesity and how to overcome it. However, Lowell says that extra heat production does not necessarily mean a rise in body temperature. “The body has several ways of maintaining a constant temperature,