Researchers from the University of Michigan were able to determine how the hormone leptin, an important regulatory substance that affects metabolism and body weight, reacts with an important receptor in the brain.
Researchers from the University of Michigan were able to determine how the hormone leptin, an important regulatory substance that affects metabolism and body weight, reacts with an important receptor in the brain.
Leptin is a protein hormone produced in fat cells and adipose tissue and has been at the focus of scientists' research regarding obesity and type 2 diabetes since its discovery in 1995. Similar to the important hormone insulin, leptin plays a central role in regulating energy consumption and production, when there is a lack of this substance or Resistance to it has been linked to obesity in humans.
Although there are several complex reasons for the existence of leptin resistance, in some cases the cause is a malfunction of the leptin receptor, found in the brain. The ability to understand the interaction between leptin and its receptor could lead to the development of new treatments in the fight against obesity and against metabolic disorders, but the structure of this signaling coupling has eluded researchers for many years.
Professor Georgios Skiniotis, from the Department of Biological Chemistry at the University of Michigan, used an electron microscope to obtain the first ever picture of the interaction between leptin and its receptor. The researcher also noticed a number of similarities between this receptor and other receptors from the same family, a fact that could provide insights into new directions for treatment of other hormone-related diseases.
"The results are exciting not only because they may help in the development of new drugs, but because we now better understand the array and mechanisms of signaling through this family of receptors, a finding that leads us to a completely new set of intriguing scientific questions," says the lead researcher.
In the article describing the research findings, which was published in the scientific journal Molecular Cell, the scientists describe how the receptor works with the help of two pivot arms that are able to rotate until they react with the substance leptin, which binds to them, and makes them more rigid. As soon as the two arms of the receptor become rigid they transmit a signal to an enzyme known as "Janus kinase". Several drugs have been studied for the treatment of disorders related to enzymes from this family - inhibiting the enzyme may lead to improvement in conditions such as rheumatoid arthritis, lupus, as well as metabolic disorders related to inflammatory conditions.
Explains one of the scientists: "This study may help us solve an important issue that we have been struggling with for some time. Since leptin is a major regulator of appetite, understanding how its resistance affects the development of obesity is a major challenge in our attempts to find new drugs to treat obesity and diabetes. Getting a clear picture of the mechanism by which leptin binds to its receptor can be the first step in overcoming leptin resistance."
The news about the study
