Modified Mice Stay Super-Fit -- Without Exercise

Bijal Trivedi
for National Geographic News
August 25, 2004

If there were a rodent Olympics, the "marathon mice" in Ronald Evans's lab would be disqualified for gene doping.

Evans and a team of researchers have genetically engineered mice that can run twice as far as their unaltered brethren. The mice also stay in peak condition, even without exercise or a good diet.

"These mice are in inherently good shape," said Evans, a hormone expert at the Salk Institute for Biological Studies in La Jolla, California. "They look like Lance Armstrong without ever getting on a bike."

The super-rodents can run farther and about an hour longer than average mice. The new rodents also appear to resist weight gain in the complete absence of exercise—even when fed a high-fat diet that led normal mice to become obese.

The research is described in yesterday's online edition of the science journal Public Library of Science Biology.

"There were clues out there, so the finding is more cool than surprising," said Mitchell Lazar, an endocrinologist not involved in the study. "These mice are really Schwartzenegger mice. They have increased muscle, low fat, and high endurance," said Lazar, who directs the Penn Diabetes Center at the University of Pennsylvania School of Medicine in Philadelphia.

The high endurance and increase in musculature in the marathon mice arose serendipitously while Evans and his colleagues studied a family of three proteins that influence how the body handles fat and sugar. The researchers found that one protein also affect muscle fibers.

The family of proteins—called peroxisome proliferator activated receptors, or PPARs—come in three types: alpha, gamma, and delta. The alpha class lowers blood fat and cholesterol. The gamma class mediates insulin control of blood sugar. But the role of the delta class in the body was largely unknown.

No Sweat

To learn more, the researchers engineered mice in which a gene produced a form of the delta protein that was permanently "on." Based on previous studies, the team hypothesized that increased activity of PPAR-delta in the muscles of the mice would allow them to burn more fat.

The experiment revealed that the genetic tweaking, indeed, rendered the mice resistant to weight gain. But the more intriguing find, researchers said, was how this change occurred. "The real surprise was that it did so by increasing the amount of slow-twitch muscle," Evans said.

Slow-twitch muscles, like the heart and diaphragm, burn fat and resist fatigue. Such muscles are important for providing energy for sustained, high-endurance activities like long-distance running, let alone regulating blood circulation and breathing.

Continued on Next Page >>




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