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Implantable 'gene circuit' helps obese mice slim down

02 December 2013

By Dr Lux Fatimathas

Appeared in BioNews 733

An artificial 'gene circuit' implanted in obese mice promotes weight loss by reducing appetite, while having no effect when implanted in mice of normal weight. The researchers say that insights from this prototype implant may prove useful in the design of devices to reduce human obesity in the future.

Professor Martin Fussenegger from ETH-Zurich, Switzerland, who led the study, said that the mice carrying the implant 'lost weight although we kept giving them as much high-calorie food as they could eat'.

The device was designed to constantly measure blood levels of fatty acids, the breakdown products of dietary fat (a high fat diet results in increased levels of fatty acids in the blood).

When high fatty acid levels were detected, the implant expressed the synthetic hormone pramlintide, which suppresses appetite through its action on a part of the brain called the hypothalamus.

The key component of the device is a lipid-sensing receptor (LSR), made by fusing parts of two different proteins together; one part that binds fatty acids and one part that binds a specific DNA sequence responsible for controlling the expression of pramlintide.

The device also contains the pramlintide gene, packaged alongside the LSR into human cells that are inserted into specially designed capsules.

The capsules were implanted in obese mice fed a high fat diet or control mice fed a normal diet. Following implantation, the obese mice began to eat less food, despite being presented with the same high fat diet, resulting in significant weight loss.

This in turn caused fatty acid levels in the blood to drop back down to normal, which switched off the implanted gene circuit and prevented further suppression of their appetites. The control mice did not show any weight loss or reduction in appetite.

Professor Sir Stephen O'Rahilly from the University of Cambridge, UK, who was not involved in the study, told the Press Association: 'This is a nice trick and is elegant technology, but its likely applicability to humans in the near future is low'.

He continued: 'To adapt this for human use a number of hurdles would need to be overcome'. These include a means of safely packaging the device to persist in the human body without being destroyed or rejected, and determining how effective the device would be given that the hormone pramlintide 'is only modestly effective for weight loss in humans, much less so than in mice'.

Worldwide, obesity has doubled since 1980 and now affects both developed and developing nations. Obesity is generally defined as having a body mass index of 30 or more and is associated with an increased risk of developing a host of health problems, including cardiovascular disease, joint problems, type 2 diabetes and certain cancers.

SOURCES & REFERENCES
Nature Communications | 26 November 2013
 
Mail Online | 27 November 2013
 
Yahoo! News | 26 November 2013
 
EurekAlert! (press release) | 26 November 2013
 

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