Modified Mice Stay Super-Fit -- Without Exercise

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Most muscles in the human body, however, are fast-twitch muscles. These fibers are essential for providing bursts of energy during short sprints or similar activities. But the muscles also burn sugar and tend to fatigue quickly.

Slow-twitch muscles avoid fatigue, because they contain many more mitochondria—"power plants" in cells that convert fat into energy.

The altered mice with extra slow-twitch muscle fibers were resistant to obesity because those muscle fibers burn fat more rapidly. Fast-twitch muscles, by contrast, have fewer mitochondria and get more of their energy from glucose, a type of sugar obtained from carbohydrates during digestion.

Athletes know that building slow-twitch muscle comes from endurance training and regular exercise. But mice with extra PPAR-delta activity were naturally endowed with a higher proportion of this endurance-enhancing, slow-twitch muscle fiber.

New Wonder Drugs?

Evans said that it was surprising to find that altering the activity of a single gene could trigger such dramatic and wide-ranging physical changes.

Under normal conditions, raising physical endurance is a complex process. Increases in muscle mass must also be accompanied by changes in blood circulation, heart activity, and the nervous system.

"But one change [PPAR-delta] seems to rewire the whole system," Evans said.

The scientist tested the endurance of the "marathon mice" by placing them on a treadmill and making them run. The mice ran about 1.1 miles (1.8 kilometers). Normal mice ran less than half that distance before reaching exhaustion.

Evans's findings on the effects of PPAR-delta proteins and the link to obesity-prevention could lead to new classes of drugs for type II diabetes, heart disease, and other obesity-related illnesses.

"Anything that helps people lose weight is good, because it increases the insulin response and produces better glucose levels, which is good for diabetics," Evans said.

Lazar, the University of Pennsylvania endocrinologist, agreed that the new research holds exciting potential for new drug development.

Medications that target the alpha and gamma classes of PPAR proteins already exist. This may pave the way for the development of new drugs that regulate PPAR-delta.

Lazar noted that if the new research can translate to humans, drugs that mimic PPAR-delta might help people who have lost muscle to cancer, aging, or malnutrition.

"It could also rescue the couch potato. In the U.S. we eat too much and don't exercise enough," Lazar said. Potential new drugs could help people "build muscle and prevent obesity without breaking a sweat," he said.

Evans added that such drugs may interest athletes seeking to boost their performance by adding slow-twitch muscles.

But for now the technology is limited to producing mightier mice.

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