The way in which the hormone leptin, an important regulator of metabolism and body weight, interacts with a key receptor in the brain has been determined by researchers at the University of Michigan. 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.
"It is exciting not only because it might help with developing new drugs," Skiniotis said. "We now better understand the design and mechanisms of signaling through this class of receptors, which brings us to a whole new set of intriguing questions."
In the paper "Ligand-Induced Architecture of the Leptin Receptor Signaling Complex," published electronically ahead of print on Oct. 11 in Molecular Cell, Skiniotis and his co-authors explain how the receptor is formed by two hinged legs that can swivel until they encounter leptin, which binds to the legs and makes them rigid.
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Alan Saltiel, director of the Life Sciences Institute and a widely cited researcher who works on diabetes, obesity and metabolic disorders, sees a range of possibilities in the work of Skiniotis.
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Source-Eurekalert