DENVER-New ways of regulating a protein that binds to DNA in fat cells could lead to treatments for obesity, diabetes and heart disease in the future. Researchers have long known that obesity can result from fat cells increasing in volume-recent studies suggest that fat cells also increase in number-although until this discovery it was unknown what regulated the development of new fat cells. Understanding these controls may be key to the treatment of obesity.
"This protein, CREB, is vital in the creation and maintenance of fat cell development," said Dwight J. Klemm, Ph.D., associate professor at National Jewish Medical and Research Center and lead author of the article announcing the finding in the February issue of the prestigious scientific journal, Molecular and Cellular Biology.
Researchers at National Jewish and the Denver Veteran's Affairs Medical Center have discovered a new way to control fat cell development, which could have important implications for the treatment and management of obesity and related diseases, like heart disease and diabetes. The discovery is the culmination of more than 3 years of research into the behavior of fat cells, and the agents that control their growth and development.
"Although much of society believes that all fat is bad, most fat cells are an important component in the regulation of the body's metabolism," said Jane E.B. Reusch, M.D., assistant professor of Medicine at the University of Colorado Health Sciences Center and Denver Veteran's Affairs Medical Center and co-author of the article. "For example, mature fat cells tell your brain you don't need to eat. This message gets misinterpreted in obesity."
Immature fat cells play a role in causing obesity by sending signals to the brain that a person is hungry. In people who are obese, fat cells become stuck in an immature state that doesn't seem to decrease appetite as effectively, causing the body to create additional fat cells. Using a negative version of cyclic adenosine monophosphate response element binding protein (CREB), researchers were able to regulate fat cell development by inserting the protein into fat cell DNA. When negative CREB is inserted into fat cells it prevents normal CREB from binding to DNA in the fat cell. By doing this, the development of new fat cells can be inhibited.
"Fat cell development is an intensive area of research in obesity," Dr. Klemm said. "This research also has potentially substantial benefits for people with diabetes and heart disease."
Obesity is the result of numerous and interacting behavioral, physiological and biochemical factors, and is a major health concern in the United States and other nations. More than 33 percent of all Americans are overweight, and excess body fat contributes to the development and seriousness of other diseases, such as heart disease and diabetes.
"We are very excited about this discovery because understanding that this protein controls fat cell development could help us develop new strategies to treat obesity and related diseases," Dr. Reusch said.
Researchers now will begin using CREB to treat obesity in laboratory animals in an effort to discover ways the protein can be safely and effectively used in medical treatments for humans.
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Journal
Molecular and Cellular Biology