Issue 214 Item 7 Key Discovery Found; Implications for New Approaches for Obesit

The discovery of a new receptor, called T-cadherin, could pave the way for new approaches to combating diabetes and obesity. Scientists have identified a receptor for adiponectin, a hormone made by fat cells that helps regulate blood sugar and fat metabolism and that is reduced in the serum of individuals who are obese or have adult-onset diabetes.

Dr. Christopher Hug from the Whitehead Institute of Biomedical Research in Cambridge, Massachusetts and colleagues report their discovery in the June 21st PNAS Early Edition. In diet-induced obese and diabetic mice, injection of adiponectin induces weight loss and improves blood sugar control, they note. The mechanism by which adiponectin influences metabolism is not fully understood but is believed to involve stimulation of fatty acid oxidation in muscle and liver.

Using expression-cloning to look for molecules that bind to adiponectin, Dr. Hug’s team found that adiponectin binds strongly to T-cadherin, a cell-surface receptor located on endothelial and smooth muscle cells, sites known to respond to adiponectin.

"Because T-cadherin is a glycosylphosphatidylinositol-anchored extracellular protein, it may act as a coreceptor for an as-yet-unidentified signaling receptor through which adiponectin transmits metabolic signals," the team suggests.
"From a clinical standpoint, the Western world, and increasingly the developing world, is experiencing an increase in obesity and diabetes." "The significant long-term complications of these conditions are primarily related to increased atherosclerosis and vascular disease, leading to heart disease, kidney disease, and stroke."

"Any insight into ways to combat these conditions would be very important, and identifying T-cadherin as a receptor for adiponectin may help in this research," he said. Knowing the target of adiponectin may permit the development of anti-obesity and anti-diabetic drugs, he added. Proc Natl Acad Sci USA 2004.

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