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drug development
How to lose weight without exercising It sounds too good to be true, but scientists have developed a molecule that effectively acts as an exercise mimic. By tricking cells into thinking they have run out of energy, the molecule increases glucose uptake and metabolism, thus improving glucose tolerance and weight loss.
D
eveloped at the University of
normal diet were treated with compound 14, their
Southampton, the molecule ‘compound 14’
blood glucose levels and weight remained normal.
inhibits the function of a cellular enzyme called
However, a single dose of compound 14 lowered
ATIC, which is involved in metabolism. This leads
the elevated blood glucose of the obese mice to
to the build-up of a molecule called ZMP in cells,
near normal levels. Furthermore, a daily dose of
which makes cells think that they have run out of
compound 14 administered to these mice for seven
energy by activating the cell’s central energy sensor,
days resulted in improved glucose tolerance and
known as AMPK.
1.5 g weight loss (about 5% body weight).
“There is a lot of evidence from previous
“Current treatments for type 2 diabetes centre
studies that if you could selectively activate AMPK
on elevating circulating insulin levels or improving
with a small molecule, it could have potential
the insulin sensitivity of an individual,” noted study
benefits in the treatment of several diseases,
co-author Dr Felino Cagampang. “The issue is that
including type 2 diabetes, by acting as an exercise
established drugs do not successfully enable patients
mimetic and increasing the uptake and usage
with type 2 diabetes to achieve glycaemic control
of glucose and oxygen by cells,” said Professor
and some can even result in weight gain, a leading
Ali Tavassoli, whose research team developed
factor driving the diabetes epidemic. In contrast,
compound 14. “Our molecule, which activates
this new molecule seems to reduce glucose levels
AMPK by altering cellular metabolism, therefore
and at the same time decrease body weight, but
holds much promise as a potential therapeutic
only if the subject is obese.” The next step for the researchers is to examine
agent.”
Professor Ali Tavassoli.
38 | LAB+LIFE SCIENTIST - September 2015
Writing in the journal Chemistry and Biology,
the molecule’s mode of action in improving glucose
the team outlined how the molecule was given to
tolerance and in reducing body weight long term.
two groups of mice — one group having been
If it is found to be safe, a drug could be developed
fed a high-fat diet which made them obese and
which would help those with diabetes and obesity
impaired their glucose tolerance. When mice with a
manage their condition.
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