BYU scientists isolate exercise 'switch'

The more you exercise, the more you can exercise — for longer times with less fatigue. Now BYU scientists say they've found at least one reason that's true — a specific enzyme that triggers the building of more "power plants" to fuel the muscles.

Their findings are in the latest Journal of Applied Physiology.

Mitochondria are those power plants, converting food into a form of energy that allows muscles to contract, said William W. Winder, a physiologist at Brigham Young University, who led the research. It's well known that repeated exercise increases the amount of mitochondria in muscles. The researchers set out to understand how that happens.

The enzymes in the mitochondria are coded by genes, so they sought the switch to turn the process on. What they found was a cellular signal that kicks off mitochondria production. When they stimulated the enzyme AMPK in mice, the mice developed more muscle mitochondria. And they found the enzyme changed and turned on yet another protein, CREB, which acts as what the researchers call a "master switch" to increase muscle mitochondria.

Winder's lab discovered the role of AMPK in muscle a dozen years ago and reported that it stimulates sugar uptake into the muscle and the burning of fat. The new research shows that each time a muscle contracts, AMPK is activated and plays a role in energy production, changing the CREB protein so it turns on the gene to make mitochondria and other enzymes of metabolism.

"The exciting thing is the CREB molecule has a large number of functions in the body, including in the brain to control appetite and for the storing of information — memory." It's involved in turning on proteins that control the adrenal and thyroid glands, among others.

That AMPK can regulate CREB, which impacts so many parts of the body, "is really quite exciting because of the number of processes AMPK could be involved in regulating."

Winder likens the importance of such molecular-level understanding of the body to repairing a car. You can't do it if you don't know how parts, such as the battery and alternator and water pump, interact. When you know, you can diagnose and fix problems.

He believes there may be ramifications for people prone to develop type 2 diabetes, for example, since they're known to benefit from endurance training. Researchers know that with type 2 diabetes, muscle becomes less sensitive to insulin, but they don't know "the exact steps in the signaling pathway where the machine is broken."