Diabetes, asthma, heart disease share biochemical pathway due to rogue aP2 protein

A study by American and Australian researchers has found that a protein previously linked to type 2 diabetes and atherosclerosis -- called aP2 -- may also be key to the development of asthma.

According to the study published in the Journal of Clinical Investigation, the protein has no useful function in the body. It only seems to appear in healthy people during diseases, and in the fat cells and macrophages (an immune cell) of people with obesity, diabetes and heart disease. The protein has also been found to negatively affect blood sugar levels and fatty acid metabolism.

"The exciting thing about this study is that perhaps the way all of these diseases are connected is through the inflammatory responses controlled by this boring little protein," said study co-author Dr. Gokhan S. Hotamisligil, of the Harvard School of Public Health in Boston.

The researchers developed genetically engineered mice, which were unable to produce aP2, to get a better idea of how the protein affects the body. These "metabolic supermice" did not develop obesity, diabetes or atherosclerosis no matter what the scientists did to promote such conditions.

Although all the work is pre-clinical, the scientists are hopeful that certain aP2-blocking drugs will be able to treat these conditions, as they produced similar effects as the genetically engineered mice, but human trials are still three to four years out.

For now, Hotamisligil said that weight control is probably the best way for people to reduce aP2 production. "AP2 tends to go along with your weight and the state of your glucose metabolism. So, if you're overweight and have asthma, losing weight might help your asthma," he said. Recent studies linking the obesity epidemic in America to the asthma epidemics support this hypothesis.

"The take-home message is that aP2 was important in acting locally in the lung," added Dr. Clifford Bassett, of Long Island College Hospital in Brooklyn, and a spokesman for the American Academy of Allergy, Asthma and Immunology. "This research may lead to future therapy to regulate or control excessive inflammation in the airway that can be associated with other forms of respiratory problems: rhinitis as well as asthma. But it's obviously preliminary data, and we need to wait for further data based upon clinical trials of drugs that work on this protein."