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Drugs Mimic Exercise and Increase Endurance

One drug active only when combined with exercise, other effective even in sedentary mice

THURSDAY, July 31 (HealthDay News) -- Two drugs can increase exercise endurance in mice by reprogramming their muscles, according to research published online July 31 in Cell. One drug is effective only in conjunction with exercise while the other is effective even in sedentary mice.

Vihang A. Narkar, from the Salk Institute in La Jolla, Calif., and colleagues examined whether drugs that activate PPAR-delta or AMPK could reprogram skeletal muscle to increase endurance in adult mice. They had previously shown that mice whose PPAR-delta gene was always on in skeletal muscle nearly doubled their endurance, and previous evidence had shown that AMPK is important in exercise physiology.

The researchers found that the PPAR-delta agonist GW1516 increased oxidative myofibers and increased endurance by 60 to 75 percent, but only when combined with exercise training, which was associated with an exercise-induced increase in AMPK. Treating mice with the AMPK agonist AICAR induced metabolic genes and increased running endurance by 44 percent without the need for exercise, even in sedentary mice.

"In this study, we revealed that synthetic PPAR-delta activation and exercise -- and, more importantly, AMPK activation alone -- provide a robust transcriptional cue that reprograms the skeletal muscle genome and dramatically enhances endurance," Narkar and colleagues conclude.

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