Another piece of obesity puzzle falls into place

Scientists have defined the structure of a key part of the human obesity receptor—an essential factor in the regulation of body fat.

The findings, reported in the journal Structure, could advance efforts to generate drugs that can both block and stimulate the receptor for the obesity hormone leptin—potentially offering new treatments for the complications of obesity and anorexia.

Leptin, the obesity hormone, is produced by fat and excess leptin predisposes overweight people to conditions such as multiple sclerosis, cancer, and heart disease. A deficiency in leptin, as occurs in malnutrition, results in infertility and immunodeficiency.

Blocking the receptor, and therefore the excessive actions of leptin, could prevent the complications of obesity, and stimulating the receptor may improve fertility and the immune response.

Researchers at the University of Sheffield solved the crystal structure of the leptin-binding domain of the obesity receptor using X-ray crystallography.

“This pioneering research gives us the potential to generate new drugs that could treat conditions and diseases associated with obesity,” says Richard Ross, professor of endocrinology.

“Modulating the actions of the obesity receptor provides a novel approach to the treatment of conditions associated with both obesity and anorexia and has the potential to make a massive difference to millions of people whose quality of life and health is hindered by obesity or malnutrition.”

Controlling appetite is a fundamental basic physiological drive that in turn is connected to many other aspects of physiology, in particular fertility and the immune response.

Pete Artymiuk, a professor in the molecular biology and biotechnology department, says: “The human obesity receptor binds the hormone leptin and together they play a key role in regulating appetite, fertility, and immunity.

“Because we now know the precise atomic structure of the receptor we can begin to design drug molecules that can alter its activity. This can be useful in the treatment of a variety of diseases ranging from obesity to autoimmune diseases including multiple sclerosis.”

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