Drug News Drugs found to boost exercise endurance
By Sue Mueller
Aug 2, 2008 - 10:39:46 AM
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Saturday August 2, 2008 (foodconsumer.org) -- Two drugs may
enhance exercise endurance in humans and potentially offer other benefits of
exercise as well, according to a new study published on July 31, 2008, in an
advance online publication in the journal Cell.
The study led by Howard Hughes Medical Institute (HHMI) researchers
at the Salk Institute for Biological Studies showed mice treated with the drugs
ran faster and longer than normal mice on treadmill tests.
Ronald M. Evans and colleagues said the drugs generate many
of the physiological effects of exercise by genetically reprogramming muscle
fibers in a way that the muscle uses energy better and can contract repeatedly
without fatigue.
In laboratory experiments, mice orally given one drug called
AICAR ran 44 percent longer than the untreated and mice when treated with
another drug GW1516 had a more drastic effect on endurance, but only when the
animals also received exercise training.
Evans said these drugs could effectively protect against
obesity and related metabolic disorders. Somehow, they can turn on genes such
that fat is preferably burned over sugar.
They could also fight devastating muscle-wasting diseases like muscular
dystrophy.
The finding of the drugs started with some genetic research
on mice.
In 2004, Evans and team
genetically engineered mice that had altered muscle composition and found the
animals had better physical endurance and were able to run twice as far as
normal mice.
The genetically altered mice also had an innate resistance
to weight gain even if fed a high fat diet. This is because the mice had
modified a gene called PPAR-delta, a master regulator of numerous genes.
Enhanced PPAR-delta activity shifted the
genetic network in muscle cells to favor burning fat over sugar as their energy
source.
The results prompted the researchers to wonder if a drug
could be used to turn on PPAR-delta in adult mice to have the same effects observed
in the genetically engineered mice.
In the current study, Evans and colleagues treated adult
mice with GW1516 for five weeks and the animals increased their endurance, but
not running performance.
However, the
mice given the drug and receiving exercise training for 30 minutes on a slow
treadmill five days a week for a total of four weeks were able to run 68
percent longer than those that received exercise training, but no drug.
The researchers explained during exercise, muscle cells uses
energy in the form of ATP and produce AMP, which triggers AMP kinase (AMPK) to
produce more ATP for the cells to burn. They found AMPK also assist PPAR-delta
to activate its gene targets. Evans explained PPAR-delta drugs affect AMPK
activity.
In another experiment, the researchers found mice treated
with the second drug AICAR run 44 percent longer than the untreated mice. But
their running performance and their ability to burn fat were not as much as
those observed in mice receiving both GW1516 and exercise training.
The benefits, according to the authors of the study, are likely
due to collaboration between cells' AMPK and PPAR-delta signaling
pathways.
Drugs alone activated a small
set of exercise-induced genes while GW1516 with exercise activated a larger group
of genes. Of these genes, many regulate metabolism and muscle remodeling.
Evans and colleagues said the drugs may offer benefits on
other systems induced by exercise such as the heart and lungs.
The drugs can potentially be used to boost athletes’
performance. Evans has developed a test to detect the substances in the blood
and urine of athletes and is now working with HHMI and the World Anti-Doping
Agency to certify the detection system that is to be used to retroactively test
athletes who compete in the 2008 Olympics.