Leptin is a protein secreted by fat cells. It was discovered by Dr. Jeffrey Friedman of Rockefeller University, who found that mice lacking the gene for leptin were unusually fat and diabetic. Leptin sends a "stop eating" signal to the brain -- a discovery that prompted the biotechnology company Amgen to pay $20 million for the rights to develop leptin as a natural way of inducing weight loss.
Now a group led by Dr. Naveed Sattar of the Glasgow Royal Infirmary says its decade-long study reveals a relationship between blood levels of leptin and the risk of heart disease."The risk associated with high levels of leptin is of the same extent associated with high blood pressure or high levels of LDL cholesterol," says Sattar, who is a senior lecturer in endocrinology and biochemistry at Glasgow. His group reports the finding in the Dec. 18 issue of Circulation: Journal of the American Heart Association.
That finding comes from a study of blood samples frozen in the 1989 West of Scotland Coronary Prevention Study, whose goal was to show that the risk of heart attacks could be reduced by a statin, a cholesterol-lowering drug.
The Scottish researchers compared leptin levels in blood samples of 377 men who had heart attacks or needed artery-opening procedures and 783 men who had no such problems.
Overall, they say, the leptin levels in the men with heart disease were 16 percent higher than in the healthy men. And each 30 percent increase in leptin levels increased the risk of heart disease by 25 percent.
Because leptin is produced by fat cells, some of that relationship comes from the well-known fact that obesity is a risk factor for heart disease, Sattar says.
"But this is telling you more than conventional measures of adipose weight," he says. "There is some evidence that leptin, as a molecule, is harmful at high levels."
In the study, high leptin levels added to the risk found in someone with a body mass index high enough to indicate obesity, Sattar says. The excess leptin indicates that a lot of that excess weight is in the form of fat rather than muscle.
High leptin levels were accompanied by high levels of another dangerous molecule, C-reactive protein, a marker for inflammation that is associated with a high risk of heart disease.
Follow-up studies are needed to verify the finding, Sattar says. "We are hoping to link up with researchers in Boston who have blood samples from women, some of whom went on to develop heart disease," he says.
Meanwhile, Amgen says it has two genetically engineered versions of leptin under trial for weight loss. Leptin, however, is not yet the magic bullet that has been hoped. Although injections of the hormone worked well in animal studies, several studies onobese humans have failed to repeat those successes.
What To Do
Until a magic diet pill comes along, eating a diet low in fat and high in fiber-rich fruits and vegetables is a basic measure for keeping weight under control and lowering the risk of heart disease, doctors say.