Scientists have developed a new drug that can mimic the beneficial effects of exercise and could boost fitness in diabetics and older adults. The rewards of aerobic exercise have long been out of reach for the elderly, obese or otherwise mobility-limited.
Building on earlier work that identified a gene pathway triggered by running, researchers have discovered how to fully activate that pathway in sedentary mice with a chemical compound, mimicking the beneficial effects of exercise, including increased fat burning and stamina. The research deepens our understanding of aerobic endurance and offers people with heart conditions, type 2 diabetes or other health limitations the hope of achieving those benefits pharmacologically, researchers said. “It’s well known that people can improve their aerobic endurance through training,” said Ronald Evans, from the Salk Institute in the US. “The question for us was: how does endurance work? And if we really understand the science, can we replace training with a drug?” Evans said.
Developing endurance means being able to sustain an aerobic activity for longer periods of time. As people become more fit, their muscles shift from burning carbohydrates (glucose) to burning fat. Researchers assumed that endurance is a function of the body’s increasing ability to burn fat, though details of the process have been murky. In the study, researchers gave normal mice a higher dose of a chemical compound called GW1516 (GW), for 8 weeks.
Both the mice that received the compound and mice that did not were typically sedentary, but all were subjected to treadmill tests to see how long they could run until exhausted. Mice in the control group could run about 160 minutes before exhaustion. Mice on the drug, however, could run about 270 minutes - about 70% longer.
For both groups, exhaustion set in when blood sugar dropped to around 70 milligrammes per decilitre, suggesting that low glucose levels are responsible for fatigue. The muscles of mice that took the exercise drug did not exhibit the kinds of physiological changes that typically accompany aerobic fitness: additional mitochondria, more blood vessels and a shift toward the type of muscle fibres that burn fat rather than sugar.
This shows that these changes are not exclusively driving aerobic endurance; it can also be accomplished by chemically activating a genetic pathway. In addition to having increased endurance, mice who were given the drug were also resistant to weight gain and more responsive to insulin than the mice who were not on the drug. “It means you can improve endurance to the equivalent level as someone in training, without all of the physical effort,” said Weiwei Fan, a research associate at Salk. The team can envision a number of therapeutic applications for a prescription drug based on GW, from increasing fat burning in people suffering from obesity or type 2 diabetes to improving patients’ fitness before and after surgery.
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