Vertebrate skeletal muscles — the kind that enable a mouse to run on a wheel or you to dash for a bus — contain two types of fibre. Type I, or 'slow-twitch', fibres are fuelled mainly by oxidative metabolism, and can contract for sustained periods. Type II, 'fast-twitch' fibres generate rapid muscle contractions but are more prone to fatigue. On page 797 of this issue, Bruce Spiegelman and colleagues (Nature 418, 797–801; 2002) describe how a protein that regulates gene expression can increase the type I fibre content, and consequently improve the stamina of isolated mouse muscles.
Previous studies have shown that the nuclear protein PGC-1α is involved in controlling genes that participate in energy metabolism in mammalian cells. This suggested that PGC-1α might play a part in muscle physiology. Indeed, Spiegelman and colleagues have now found that if the protein is expressed in mouse skeletal muscles, more of the characteristically 'redder' type I muscle fibres are formed, with fewer type II fibres. The authors show that isolated PGC-1α-expressing muscles contain proteins that are typical of type I fibres, and can sustain contraction for around twice as long as equivalent muscles from wild-type mice, in an experiment based on standardized electrically induced contraction.
These results tie in nicely with the fact that the expression of PGC-1α can be induced naturally by exercise in experimental animals, and that exercise can convert type II fibres into type I fibres. Further work will be needed to define the precise molecular signals that control PGC-1α activity and to identify the genes regulated by this protein that lead to the formation of type I muscle fibres. It may be that, in the future, drugs that influence these regulatory events will be useful in situations where muscle activity is impaired. Great care would have to be taken, however, as PGC-1α seems to be involved in many other regulatory events in the body.
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Pharmacological Reviews (2003)
The Physician and Sportsmedicine (2002)