Target for obesity drugs comes into focus

October 11, 2012
Georgios Skiniotis developed a picture of the interaction between leptin and its receptor using electron microscopy. The two legs of the receptor become rigid by binding to leptin and signal to an enzyme called the Janus kinase.

(Medical Xpress)—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 since it was discovered in 1995. Like insulin, leptin is part of a 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 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 at the U-M Medical School, employed 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 ," 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.

Once the two legs of a receptor become rigid by binding to leptin, they signal to an enzyme called the Janus kinase. A number of drugs have been studied for treatments related to the Janus kinases; inhibiting it may lead to improvement of conditions like rheumatoid arthritis, psoriasis and metabolic disorders that are linked to inflammation.

Alan Saltiel, director of the Life Sciences Institute and a widely cited researcher who works on diabetes, obesity and , sees a range of possibilities in the work of Skiniotis.

"This study may help solve an important issue we've been struggling with for some time," he said. "Since leptin is a master regulator of appetite, understanding why resistance to its effects develops in obesity has been a major obstacle to discovering new drugs for obesity and diabetes. Developing a clear picture of how leptin can bind to its receptor may be the first step in overcoming leptin resistance."

Explore further: New drug to tackle fat problems

Related Stories

New drug to tackle fat problems

April 27, 2012
Medical researchers at the University of Sheffield have defined the structure of a key part of the human obesity receptor- an essential factor in the regulation of body fat- which could help provide new treatments for the ...

Voluntary exercise by animals prevents weight gain, despite high-fat diet

May 18, 2011
(Medical Xpress) -- University of Cincinnati (UC) researchers have found that animals on a high-fat diet can avoid weight gain if they exercise.

Modulation of inhibitory output is key function of antiobesity hormone

July 13, 2011
Scientists have known for some time that the hormone leptin acts in the brain to prevent obesity, but the specific underlying neurocircuitry has remained a mystery. Now, new research published by Cell Press in the July 14 ...

New drug could help maintain long-term weight loss

July 26, 2012
A new drug could aid in losing weight and keeping it off. The drug, described in the journal Cell Metabolism on July 26, increases sensitivity to the hormone leptin, a natural appetite suppressant found in the body. Although ...

Recommended for you

Study reveals new mechanisms of cell death in neurodegenerative disorders

November 22, 2017
Researchers at King's College London have discovered new mechanisms of cell death, which may be involved in debilitating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

Researchers find infectious prions in Creutzfeldt-Jakob disease patient skin

November 22, 2017
Creutzfeldt-Jakob disease (CJD)—the human equivalent of mad cow disease—is caused by rogue, misfolded protein aggregates termed prions, which are infectious and cause fatal damages in the patient's brain. CJD patients ...

Surprising roles for muscle in tissue regeneration, study finds

November 22, 2017
A team of researchers at Whitehead has illuminated an important role for different subtypes of muscle cells in orchestrating the process of tissue regeneration. In a paper published in the November 22 issue of Nature, they ...

How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis

November 21, 2017
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.