Molecular Switch Controls Muscle Fiber Type

Investigators have found that peroxisome-proliferator-activated receptor-co-activator-1 (PGC-1), which is expressed in several tissues including brown fat and skeletal muscle, may be the molecular switch that converts easily fatigued "fast-twitch” muscle fibers into durable, oxygen-fueled "slow-twitch” fibers. The discovery was reported in the August 15, 2002, issue of Nature.

In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibers are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibers. Most muscles contain a combination of the two fibers.

PGC-1, a molecule known as a "transcriptional co-activator,” had previously been shown to act as a switch in the liver to regulate the manufacture of glucose. To study its role in muscle, researchers from the Dana-Farber Cancer Institute (Boston, MA, USA) developed a line of transgenic mice that carried the PGC-1 gene in all their skeletal muscles.

They found that when PGC-1 was expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fiber-type conversion took place. Muscles normally rich in type II fibers were redder and activated genes of mitochondrial oxidative metabolism. Furthermore, an endurance test showed that the muscles that had been treated with the PGC-1 genes contracted efficiently for seven minutes, while muscles from untreated mice worked efficiently only for about two minutes.

"PGC-1 appears to be the switch, or a major component of it, that enables your body's muscles to adjust to the demands being put on them,” explained Dr. Bruce M. Spiegelman, cell biologist at the Dana-Farber Cancer Institute and the study's senior author. "Understanding how this system works could make it possible to develop a drug to manipulate this system. These findings in time may benefit people with Type 2 diabetes, as the Type I muscle is more responsive to insulin in regulating blood glucose levels.”