A relative of the anti-aging gene Klotho helps activate a hormone that can lower blood glucose levels in fat cells of mice, making it a novel target for developing drugs to treat human obesity and diabetes, UT Southwestern Medical Center researchers have found.
In a study available online and in the Proceedings of the National Academy of Sciences, the researchers show that a type of Klotho protein binds to receptors for a metabolic hormone in fat cells, forming a "co-receptor" that enables the hormone to stimulate the processing of glucose, the body's main source of fuel. The Klotho gene has previously been found to play a role in prolonging the life of mice partly by controlling insulin.
Mice lacking this particular Klotho protein can't stimulate this key metabolic activity, said Dr. Makoto Kuro-o, associate professor of pathology at UT Southwestern and the study's senior author.
"The ability to stimulate the glucose processing is key to proper metabolism, so this Klotho protein, known as beta-Klotho, is a novel target for developing drugs that can enhance or block the metabolic activity of this hormone, which has been shown to be able to lower blood glucose in mice," he said. "Klotho's role in regulating the metabolic activity of the growth hormones is essential."
Dr. Kuro-o and his colleagues originally discovered the Klotho gene in 1997, naming it after one of the mythical Greek characters who controlled the length of human life.
The Klotho protein, which is found in several species, acts as a hormone in mice, circulating through the blood and binding to cells. Previous studies have shown that mutant mice lacking the Klotho gene appear normal until about a month of age, and then begin showing signs of age, such as skin atrophy, osteoporosis, arteriosclerosis and emphysema. The mice die prematurely at about two months.
Therapies based on Klotho could prove to be a way to extend life or slow the effects of aging, so Dr. Kuro-o and his colleagues are trying to uncover more about how Klotho works.