Genetic engineering supplants exercise

Marathon mice created: They're athletic despite inactivity, high-fat diet

August 24, 2004|By Jamie Talan | Jamie Talan,NEWSDAY

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 its littermates - it runs twice as far as expected.

"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 the findings could have implications for athletes and people 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.

The finding suggests that one gene, PPAR-delta - a master gene that controls several others - is designed to regulate muscle development. Enhancing the gene's 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 today in the Public Library of Science Biology journal.

Earlier, 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 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 other animals - an extra hour, Evans said, for the equivalent of a mile.

While researchers altered the gene to make more protein, they tested benefits of an experimental medicine that increases the protein in other mice.

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.

Today's study is the latest to examine how animals' athleticism can be altered. In a study published last year, scientists bred 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 Veterans Administration Medical Center in Portland, Ore., spent years measuring the movement of animals on a running wheel. The animals with the longest records were mated and, after 32 generations, four separate lines of animals were produced 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, University of Wisconsin's Stephen Gammie said. But their blood had higher levels of the stress hormone cortisol.

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 neurons in this region.

Newsday is a Tribune Publishing newspaper.

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