The hormone leptin is only on the list of proteins that appear to play a key role in regulating weight gain. One of its partners is a protein called agouti, previously known for his role in the regulation of coat color in mammals (see Science NOW, January 3, and Science February 7, p 751. *). Now a new mouse model described in the current issue of Proceedings of the National Academy of Sciences , can help researchers understand the role of the agouti in body weight regulation - for information that can lead to new drugs for the treatment of obesity.
previous evidence implicating agouti in weight control comes from a mutant mouse strain that produces natural agouti in all tissues, so that it becomes not only obese but also developing diabetes due to insulin resistance. Normal mice are only the protein in hair cells, however. In contrast, humans, even those of normal weight, express the gene in their fat cells, where its function is currently unknown.
To get a better idea of what agouti made in fat cells, Rick Woychik and colleagues at Oak National Laboratory Ridge in Tennessee first joined the agouti gene to a regulatory sequence that causes the gene to be turned on in the adipose tissue. They transferred then this hybrid gene in normal mouse embryos, which then grow to the protein in their fat cells. As with the normal humans, these transgenic mice do not become obese. But they did it when scientists gave them injections of insulin, a hormone that helps cells use simple sugars. The animals that received daily insulin injections for 1 week earned 1.7 times as much weight as non-transgenic animals given the same amount of food.
"This suggests that agouti gene plays a role in adipose tissue function and the [protein] acts synergistically with insulin to promote weight gain," says Woychik . Indeed, it suggests that in obese agouti naturally occurring mutants, abnormal protein production can indeed stimulate excessive insulin production by the pancreas, which could then not only help to ensure that the gain of the weight of animals, but also lead to resistance to the possible insulin and diabetes.
Exactly how agouti and insulin interact on adipose tissue "is the great issue, "says George Wolff, a geneticist at the National Center for toxicological research in Jefferson, Arkansas. and find the answer, Wolff added, is likely to be difficult, because the system involved in regulating weight is" very complicated and complex. " However, with this new mouse molecular engineering should help scientists trace the complex ways in fat regulation, Woychik said. Once these channels are known, it adds, it is possible to develop drugs that stimulate or block to trigger the gain or weight loss.
* For details, Science Online subscribers can connect the full text of the news story.
0 Komentar