Target for obesity drugs comes into focus

Researchers at the University of Michigan have determined how the hormone leptin, an important regulator of metabolism and body weight, interacts with a key receptor in the brain.

Leptin is a hormone secreted by fat tissue that has been of interest for researchers in obesity and Type 2 diabetes since it was discovered in 1995. Like insulin, leptin is part of a regulatory network that controls intake and expenditure of energy in the body, and a lack of leptin or resistance to it has been linked to obesity in people.

Although there can be several complex reasons behind leptin resistance, in some cases the underlying cause is malfunction of the leptin receptor in the brain. An understanding of how leptin and its receptor interact could lead to new treatments for obesity and metabolic disorders, but the structure of this signaling complex has evaded researchers for years.

Georgios Skiniotis, a faculty member at the Life Sciences Institute and assistant professor in biological chemistry at the U-M Medical School, employed electron microscopy to obtain the first picture of the interaction between leptin and its receptor.

Skiniotis also traced similarities between the leptin receptor and other receptors of the same family, which may provide insight into new targets for treatment of other hormone-related diseases.