Johns Hopkins scientists exploit novel route to reverse enlarged hearts in ...( Working on genetically engineered obese...),Health

Leptin is a protein hormone made by fat cells that signals the brain to stop eating. Alterations in the leptin-making gene may create leptin deficiency linked to obesity and other defects in weight regulation.

By injecting so-called ciliary neurotrophic factor (CNTF) into mice that were either deficient in or resistant to leptin, the researchers reduced the animals' diseased and thickened heart muscle walls by as much as a third and the overall size of the left ventricle, the main pumping chamber, up to 41 percent, restoring the heart's architecture toward normal.

Enlarged hearts lead to heart failure and death. Results of the study, supported in part by the National Institutes of Health, are to be published in the March 6 issue of the Proceedings of the National Academy of Sciences.

"These findings suggest there's a novel brain-signaling pathway in obesity-related heart failure and have therapeutic implications for patients with some forms of obesity-related cardiovascular disease," says study senior author Joshua M. Hare, M.D., a professor and medical director of the heart failure and cardiac transplantation programs at The Johns Hopkins University School of Medicine and its Heart Institute.

Most obesity in people is associated with an inability to use leptin made naturally in the body, says Hare, who also is director of the cardiovascular section of Hopkins' Institute for Cellular Engineering.

"We knew that leptin supplements wouldn't address obesity-linked heart disease, but reasoned that CNTF might be a way to get around leptin resistance by activating a related signaling pathway with similar effects on bo
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Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
6-Mar-2006