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Biological Chemistry

Gene Activators Mimic Effects Of Exercise

Small-molecule drugs help burn fat and enhance endurance in mice by remodeling muscle

by Sophie L. Rovner
August 4, 2008

Couch potatoes, rejoice! A research team led by Howard Hughes Medical Institute investigator Ronald M. Evans of the Salk Institute for Biological Studies, in La Jolla, Calif., has identified two compounds that increase the ability of muscle cells to burn fat and that significantly improve endurance for physical activity in mice (Cell, DOI: 10.1016/j.cell.2008.06.051). The compounds could aid obese people and patients who suffer from muscle-wasting diseases such as muscular dystrophy.

A group led by Evans had previously shown that genetic engineering of mice to enhance the activity of the PPARδ gene modified their muscle composition and enabled the animals to run twice as far as normal mice. Now, Evans and coworkers have determined that the investigational drug GW1516 reproduces this effect in normal mice but only if the mice exercise. The researchers found that another compound, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), boosts endurance even in mice that are not put on an exercise regimen. AICAR activates muscle genes that are normally turned on by exercise.

Recognizing that athletes might abuse these drugs, the team is developing a mass spectrometry technique to detect the compounds and their metabolic by-products in blood and urine.


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