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How leptin contributes to obesity

15th October 2012

Researchers from the University of Michigan say they have gained new insight into the way that the hormone leptin, which regulates metabolism and body weight interacts with an important brain receptor.

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Published in the journal Molecular Cell, the findings shed new light on possible ways to combat obesity, metabolic disorders, and some inflammatory diseases.

Scientists are hoping that leptin--a hormone that helps the body regulate appetite--could point the way to new treatments for type 2 diabetes. The hormone was only discovered in 1995, and has attracted great research interest because it governs how energy is used up in the body.

As well as resistance to the sugar-regulating hormone insulin, obese people often also show leptin resistance, or not enough leptin, as well.

The researchers write that the reasons behind leptin resistance are complex. It can be triggered when the leptin receptors in the brain malfunction, for example.

Using electron microscopy, a research team led by Georgios Skiniotis formed the first molecular-level picture of how leptin interacts with its receptors.

Previously, the chemical signals involved in this interaction have not been well understood.

They discovered that the leptin receptor is actually very similar to other receptors of the same type, paving the way for potential new treatments targeting hormones in obesity, diabetes, and other hormone-related conditions.

Skiniotis said the findings were exciting because they might help with developing new drugs, but also because scientists now had a better understanding of the design and mechanisms of signalling employed by this type of receptor, which is formed at a microscopic level by two swiveling hinged legs, which carry on swiveling until they come into contact with leptin.

The legs become rigid as soon as leptin binds to the receptor, and send a signal to an enzyme known as the Janus kinase.

Inhibition of this enzyme could target diseases linked to inflammation, like rheumatoid arthritis, type 2 diabetes and psoriasis.

According to Alan Saltiel, director of the University's Life Sciences Institute, the research could help scientists understand how leptin resistance develops, which has been a major obstacle in the development of new drugs for diabetes and obesity.

Previous studies have already identified a signalling pathway in the brain which may induce leptin resistance at a cellular level, which means that the body fails to understand that it is full and does not stop eating.

They have also shown that eating too much fructose, a simple sugar found in fruit and fruit juice, as well as in some processed foods, can lead to leptin resistance.


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