http://www.nynewsday.com/news/health/ny-hsmouse0824,0,7562101,print.story?coll=n
y-health-headlines

The subject of this post is an embellishment, but the results so far
are very interesting.

Should we be looking to being fit, lean, and strong couch potatoes?
Would you take a drug that would make you lean, strong and boost your
endurance? I would, if there was no side effects.

``The animals given the drug experienced the same muscle and metabolic
benefits of the genetically-bred mice, including protection against
weight gain.''

i
not quite holding his breath
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Gene research creates a 'Mighty Mouse'
                     
                     
                     
                     
                               
BY JAMIE TALAN
Staff Writer

August 23, 2004, 2:44 PM EDT

Increasing the activity of a single gene turns a mere rodent into
Mighty Mouse, according to a new study.

California scientists have genetically engineered an animal that has
more muscle, less fat and more physical endurance than their
littermates. The mice go twice as far as expected. They also seem
protected against the inevitable weight gain that follows a high fat,
high calorie diet.

"We were quite surprised," said Ronald M. Evans, a Howard Hughes
Medical Institute investigator at the Salk Institute in La Jolla,
Calif. "Most people think that increased endurance comes from
training. But we've been able to re-create this entire exercise
network by increasing the activity of a single protein."

Evans said that the findings could have implications for human
athletes and others who shy away from exercise despite the known
benefits for the cardiovascular system, the muscles and bones, and
even the brain. "While it could be used for patients who can't
exercise, it could also be abused by athletes to enhance performance,"
said Evans.

Nonetheless, the finding suggests that one gene, called PPAR-delta, is
designed to regulate muscle development. In turn, strong muscles have
positive effects on other body systems. Scientists modified the
PPAR-delta gene to express, or make, more protein.

The PPAR-delta is a master gene that regulates several other
genes. Enhancing its activity created animals with attributes
associated with extensive physical training.

Evans and his colleagues suspect that enhancing muscle development
alters the fat-burning and muscle-making machinery of the body. The
study appears Tuesday in the Public Library of Science Biology
journal.

In earlier work, the scientists showed that activating PPAR-delta
helped animals burn more fat. In the latest studies, they found that
the protein also alters the structure and function of muscle fibers,
making them more resistant to fatigue. The enhanced protein also
allows the animals to keep trim despite a diet rich in fat and
calories.

On an exercise wheel, the genetically engineered mice ran twice as
long as the normal animals -- an extra hour, Evans said, for the
equivalent of a mile.

While researchers altered the gene to make more protein, they also
designed a study to test the benefits of an experimental medicine that
increases the protein. The animals given the drug experienced the same
muscle and metabolic benefits of the genetically-bred mice, including
protection against weight gain. The experimental drug, developed by
GlaxoSmithKline, is now in clinical studies to test its safety and
effectiveness in pre-diabetes conditions.

The new study is the latest to examine how animals' athleticism can be
altered. In a study published last year, scientists created the next
generation of athletic mice -- animals that ran three times farther
and faster than usual.

"They are born to run," said neuroscientist Justin Rhodes. The study
appeared in the journal Behavioral Neuroscience. "Give them a wheel
and they want to run faster and more intensely than the other
animals."

Rhodes, at the Veteran's Administration Medical Center in Portland,
Ore., spent years measuring the movement of animals on a running
wheel. Then, in collaboration with University of Wisconsin's Stephen
Gammie and Ted Garland of the University of California at Riverside,
Rhodes mated animals with the longest records. After 32 generations,
they had four separate lines of animals that were faster and capable
of running farther.

These animals didn't have better hearts, stronger muscles or more
robust oxygen consumption than non-runners, Gammie said. But they did
have higher levels of the stress-hormone cortisol in their blood. In
addition, areas of the brain that regulate motivation were far more
active and a brain area known to give birth to new brain cells in
adults went into overdrive, producing 30 percent more new neurons in
this region.

Gammie said that these findings could prove what scientists have long
suspected: That exercise is naturally rewarding.

In that study, half the mice were given unlimited access to the
running wheel for six straight days. On the seventh day, only half of
these were allowed to use the wheel.

Researchers found a correlation between how much the animals had run
and the activity in certain parts of the brain. And brain regions
involved with motivation and movement registered more activity in the
animals that didn't get to run on the seventh day, suggesting that the
motivational circuits were craving the next opportunity, Rhodes said.

Genetic tests in the mice suggest that a gene that regulates the brain
chemical dopamine may be involved in this enhanced running
ability. Dopamine is a key chemical that regulates motivation and
reward, as well as movement. The animals ran into old age but didn't
live any longer than their normal littermates.