Jeffrey Friedman receives Shaw Prize for discovery of leptin

Jeffrey M. Friedman, Marilyn M. Simpson Professor and head of the Laboratory of Molecular Genetics at Rockefeller University, has received the 2009 Shaw Prize in Life Science and Medicine. The prize was announced today by the Hong Kong-based Shaw Prize Foundation.

Friedman shares the $1 million award with Douglas L. Coleman, emeritus scientist at The Jackson Laboratory, for their work leading to the discovery of leptin, a hormone that regulates food intake and body weight.

Prior to Friedman's groundbreaking research, little was known about the components of the biologic system that controls weight, with many scientists questioning the very existence of such a homeostatic system. The discovery of leptin provided a genetic explanation of obesity and has challenged the popular belief that lack of willpower causes people to be obese.

With the discovery of leptin and Friedman's subsequent studies, the logic of an entirely new physiological system has been established with direct implications for the pathophysiology of human obesity. In addition to providing scientists with a new target for treating obesity, the discovery has helped scientists develop treatments for other metabolic conditions, such as diabetes, and for women with hypothalamic amenorrhea.

In December 1994, Friedman, who also is an investigator at the Howard Hughes Medical Institute, and his colleagues published a landmark paper in the journal Nature, in which they identified a gene in mice and humans called obese (ob) that codes for a hormone he later named leptin, after the Greek word leptos, for thin. Friedman and colleagues showed that leptin is a hormonal signal made by the body's fat cells that regulates food intake and energy expenditure. Leptin has powerful effects on reproduction, metabolism, other endocrine systems and even immune function.

Mice that lack ob, and thus do not produce leptin, are massively obese, weighing as much as three times the size of their normal littermates. Friedman showed that after normal and ob-deficient mice are injected with synthetic leptin, they are more active and lose weight. In addition, humans lacking leptin eat copious amounts and are massively obese. Leptin treatment of these individuals leads to massive weight loss. The dramatic effect of leptin in these patients establishes a key role for this hormone in human physiology.

However, the majority of obese people have very high levels of leptin circulating in their blood. Friedman's lab went on to show that high leptin levels are associated with resistance to leptin and provided evidence that suggests that animals destined to be obese increase their production of leptin to satisfy a higher set point for weight. These observations have reframed views on the pathogenesis of obesity and suggested that the development of approaches to improve leptin response in resistant individuals could provide new treatments for obesity.

The ob mouse was first discovered in 1950 by researchers at The Jackson Laboratory. Then in 1966, animal care technicians noticed some young mice that were much fatter than their siblings, with symptoms of diabetes. Coleman became interested in these mice, known as diabetes (db) mutant mice, for his studies of metabolic pathways.

Coleman conducted a series of experiments that led him, in 1973, to propose the existence of a "satiety factor" (later identified as leptin) that the obese mice fail to produce and that the diabetes mice produce but do not respond to. He later wrote that his work with the obese and diabetes mice "established that the severity of the diabetes was dependent on unknown modifying genes.

The Shaw Prize, known as the Nobel Prize of the East, was established by Run Run Shaw, a Chinese movie executive and philanthropist, in November 2002. The prize is an international award that honors individuals who are currently active in their respective fields and who have achieved distinguished and significant advances, who have made outstanding contributions in culture and the arts or who in other domains have achieved excellence.