Researchers in Canada, Scotland and Australia
have discovered that salicylate, the active ingredient in aspirin, directly
increases the activity of the protein AMPK (AMP-activated protein kinase), a
key player in regulating cell growth and metabolism.
AMPK
which is considered a cellular fuel-gauge is switched on by exercise and the
commonly used anti-diabetic medication metformin.
The
research from scientists at McMaster University, the University of Dundee and
the University of Melbourne will be published in today's issue of the journal Science.
"We're
finding this old dog of aspirin already
knows new tricks," said Dr. Greg Steinberg, a co-principal investigator of
the study. "In the current paper we show that, in contrast to exercise or
metformin which increase AMPK activity by altering the cells energy balance,
the effects of salicylate is totally reliant on a single Ser108 amino acid of
the beta 1 subunit.
"We
show that salicylate increases fat burning and reduces liver fat in obese mice and that
this does not occur in genetically modified mice lacking the beta1 subunit of
AMPK," he said. Steinberg is an associate professor of medicine in the
Michael G. DeGroote School of Medicine at McMaster University and the Canada
Research Chair in Metabolism and Obesity.
These
findings are important as a large clinical trial is currently underway testing
whether salsalate (a well-tolerated aspirin derivative), can preventType 2 diabetes.
Salicylate,
which is derived from willow bark, and is the active ingredient in aspirin, is
believed to be one of the oldest drugs in the world with first reports of its
use dating back to an Egyptian papyrus in 1543 BC.
An
anti-inflammatory drug first used as a painkiller more than a century ago,
aspirin is now given to people at risk of heart attacks and strokes as well as
patients with vascular disease. McMaster scientists played a key role in that
previous research.
Three
studies published last month in the medical journal The Lancet reported that
taking an aspirin every day may significantly reduce the risk of many cancers
and prevent tumors from spreading. The unanswered question was how this
anti-cancer benefit occurs.
With
many recent studies showing that metformin may be important for cancer
prevention the authors' study raise the interesting possibility that aspirin
may also be working in a similar manner; however, further studies are needed as
the concentrations of salicylate used in the current study were higher than the
cancer trials. Nonetheless, the researchers' results show the one thing that
salicylates and metformin hold in common is their ability to activate AMPK.
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