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.
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
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.