Open access, freely available online

Primer

Skeletal Muscle Fiber Type: Influence

on Contractile and Metabolic Properties
Juleen R. Zierath*, John A. Hawley

S
keletal muscle demonstrates a potential for adaptation in performance (ST), which stain dark or red, and fast-
remarkable plasticity, adapting and metabolism, as well as lead to the twitch (FT), which stain light or pale.
to a variety of external stimuli discovery of novel genes and pathways In humans, a further subdivision of the
(Booth and Thomason 1991; Chibalin in common clinical disease states. FT fibers is made (Brooke and Kasier
et al. 2000; Hawley 2002; Flûck 1970), whereby the more aerobic (or
and Hoppeler 2003), including How Is Skeletal Muscle Fiber Type oxidative) FT fiber is designated FTa,
habitual level of contractile activity Classified? and the more anaerobic (glycolytic)
(e.g., endurance exercise training), Much of our early understanding fiber is termed FTb. Under aerobic
loading state (e.g., resistance exercise of the plasticity of skeletal muscle has conditions (sufficient oxygen supply
training), substrate availability been derived from studies undertaken to the working muscles), energy is
(e.g., macronutrient supply), and by exercise physiologists (e.g., Holloszy produced without the production of
the prevailing environmental 1967). With the application of surgical lactate. Under anaerobic conditions
conditions (e.g., thermal stress). This techniques to exercise physiology in (insufficient oxygen supply to the
phenomenon of plasticity is common the late 1960s (Bergstrom and Hultman
to all vertebrates (Schiaffino and 1966), it became possible to obtain Citation: Zierath JR, Hawley JA (2004) Skeletal muscle
biopsy samples (~150 mg) of human fiber type: Influence on contractile and metabolic
Reggiani 1996). However, there exists properties. PLoS Biol 2(10): e348.
a large variation in the magnitude skeletal muscle, and by means of
of adaptability among species, and histological and biochemical analyses, Copyright: © 2004 Juleen R. Zierath and John A.
Hawley. This is an open-access article distributed
between individuals within a species. specific morphological, contractile, and under the terms of the Creative Commons Attribution
Such variability partly explains metabolic properties were identified. License, which permits unrestricted use, distribu-
the marked differences in aspects In 1873, the French anatomist Louis tion, and reproduction in any medium, provided the
original work is properly cited.
of physical performance, such as Antoine Ranvier had already observed
endurance or strength, between that some muscles of the rabbit were Abbreviations: FT, fast-twitch; FTa, aerobic FT fiber;
redder in color, and contracted in a FTb, anaerobic FT fiber; HIF-1α, Hypoxia Inducible
individuals, as well as the relationship Factor-1α; MAPK, mitogen-activated protein kinase;
of skeletal muscle fiber type slower, more sustained manner, than MEF2, myocyte enhancer factor 2; PGC-1, peroxisome
composition to certain chronic disease paler muscles of the same animal. proliferator γ coactivator 1; PPARδ, peroxisome prolif-
erator-activated receptor δ; ST, slow-twitch; VO2max,
states, including obesity and insulin These early observations formed the maximal O2 uptake
resistance. basis of the classical terminology of
In most mammals, skeletal muscle red and white muscle fibers, which was Juleen R. Zierath is with the Department of Surgical
Sciences, Section of Integrative Physiology, Karolinska
comprises about 55% of individual body subsequently found to be related to Institutet, in Stockholm, Sweden. John A. Hawley
mass and plays vital roles in locomotion, myoglobin (an iron-containing oxygen- is with the Exercise Metabolism Group, School of
transport protein in the red cells of Medical Sciences, Faculty of Life Sciences at RMIT
heat production during periods of cold University in Bundoora, Australia.
stress, and overall metabolism (Figure the blood) content (Needham 1926).
1). Thus, knowledge of the molecular Based upon histochemical staining *To whom correspondence should be addressed.
E-mail: Juleen.Zierath@fyfa.ki.se
and cellular events that regulate (Engel 1962), muscle fibers are now
skeletal muscle plasticity can define the commonly distinguished as slow-twitch DOI: 10.1371/journal.pbio.0020348

PLoS Biology | www.plosbiology.org 1523 October 2004 | Volume 2 | Issue 10 | e337 | e348
 Table 1. Contractile Characteristics, Selected Enzyme Activities, and Morphological
and Metabolic Properties of Human Skeletal Muscle Fiber Types
Characteristic ST Oxidative FTa Oxidative FTb Glycolytic
Contractile characteristics

Time to peak tension 1.0 0.4 0.4

Ca2+ myosin ATPase 1.0 3.0 3.0

Mg2+ actomyosin ATPase 1.0 2.8 2.8

DOI: 10.1371/journal.pbio.0020348.g001 Enzyme activities

Figure 1. Anatomy of a Skeletal Muscle
Individual bundles of muscle fibers are Creatine phosphokinase 1.0 1.3 1.3
called fascicles. The cell membrane
surrounding the muscle cell is Phosphofructokinase 1.0 1.5 2.1
the sarcolemma, and beneath the
sarcolemma lies the sarcoplasm, which Glycogen phosphorylase 1.0 2.1 3.1
contains the cellular proteins, organelles,
and myofibrils. The myofibrils are Citrate synthase 1.0 0.8 0.6
composed of two major types of protein
filaments: the thinner actin filament,
and the thicker myosin filament. The Morphological properties
arrangement of these two protein
filaments gives skeletal muscle its striated Capillary density 1.0 0.8 0.6
appearance.
Mitochondrial density 1.0 0.7 0.4
working muscles), energy is produced
via the glycolytic pathway, which results
Metabolic properties
in lactate accumulation and in turn
limits anaerobic exercise. Thus, muscle Oxidative potential 1.0 0.7 0.2
fibers can be classified in terms of
contractile and metabolic properties Glycolytic potential 1.0 1.5 2.0
(Table 1).
[Phosphocreatine] 1.0 1.2 1.2
All individuals have different
capacities to perform aerobic or [Glycogen] 1.0 1.3 1.5
anaerobic exercise, partly depending
on their muscle fiber composition. In [Triacylglycerol] 1.0 0.4 0.2
untrained individuals, the proportion
This table highlights the relationship between skeletal muscle fiber-type composition and the indicated
of ST fibers in the vastus lateralis muscle contractile and metabolic properties thats are consistent with differences in speed and endurance. All values are
(the largest of the quadriceps muscles expressed as a fold-change relative to ST oxidative fibers.
and the most commonly studied muscle DOI: 10.1371/journal.pbio.0020348.t001

in humans), is typically around 55%,

with FTa fibers being twice as common Does Muscle Fiber Type factor governing success in endurance
as FTb fibers (Saltin et al. 1977). While Composition Influence Athletic events was proposed (Gollnick et al.
marked differences in the metabolic Performance? 1972; Costill et al. 1976).
potentials between FTa and FTb fibers In this regard, the results of Fink
are observed in untrained humans, During the 1970s and 1980s, it was et al. (1977) are important. These
the absolute level for the activities popular to determine the muscle fiber researchers determined the fiber
of oxidative and glycolytic enzymes composition of athletes from different composition from the gastrocnemius
in all fiber types is large enough to sports events. These studies revealed muscle (the muscle of the calf of the
accommodate substantial aerobic and that successful endurance athletes have leg) of 14 elite male long distance
anaerobic metabolism (Saltin et al. relatively more ST than FT fibers in the runners, 18 good (but not world-
1977). While there is a large degree of trained musculature (Costill et al. 1976; class) male long distance runners, and
homogeneity within individual skeletal Fink et al. 1977; Saltin et al. 1977). In 19 untrained men. The elite group
muscles from rodents (Delp and Duan contrast, sprinters have muscles that are included Olympic medal winners
1996), this is not the case for humans composed predominantly of FT fibers (Figure 2) and American record
(Saltin et al. 1977). The dramatic (Costill et al. 1976). Accordingly, the holders at the time. Muscle from
heterogeneity of fiber type composition belief that muscle fiber type can predict the elite runners contained a larger
between people may explain their athletic success gained credibility. proportion of ST fibers than either the
remarkable variation in exercise In particular, the notion that the good runners or the untrained men
performance. proportion of ST fibers might be a (79.0% ± 3.5% versus 61.8% ± 2.9%

PLoS Biology | www.plosbiology.org 1524 October 2004 | Volume 2 | Issue 10 | e348

versus 57.7% ± 2.5% respectively; p to promote the nerve-dependent
< 0.05). The values found for several induction of the slow program in
of the elite runners were the highest regenerating muscle (Murgia et al.
observed in human muscle (> 92% ST). 2000). Calcineurin, a Ca2+/calmodulin-
Moreover, the ST fibers from the elite activated phosphatase implicated in
runners were 29% larger than FT fibers nerve activity-dependent fiber-type
(p < 0.05), and both ST and FT fibers specification in skeletal muscle, directly
were larger in the good runners than controls the phosphorylation state of
in the untrained men. Because of the the transcription factor NFAT, allowing
marked hypertrophy (bulk increase) for its translocation to the nucleus and
of the ST fibers in the elite runners, leading to the activation of slow-type
the cross-sectional area composed of muscle proteins in cooperation with
these fibers was greater than either the myocyte enhancer factor 2 (MEF2)
good runners or the untrained subjects proteins and other regulatory proteins
(82.9% ± 3.1% versus 62.1% ± 2.6% DOI: 10.1371/journal.pbio.0020348.g002 (Chin et al. 1998; Serrano et al. 2001).
versus 60.0% ± 2.7% respectively; p < Calcium-dependent Ca2+/calmodulin
Figure 2. Microscopic View of the
0.05). When the data from the elite and Gastrocnemius Skeletal Muscle from a World- kinase activity is also upregulated by
good runners was combined, a positive Class Marathon Runner, Frank Shorter (Olympic slow motor neuron activity, possibly
correlation between the proportion Gold Medalist, 1972; Olympic Silver Medalist, because it amplifies the slow-type
1976)
of ST fibers and the best 6-mile The darkly stained fibers are relatively calcineurin-generated responses
performance time was noted (r = −0.62, slow in contractile rate and are ST. by promoting MEF2 transactivator
p < 0.05). These fibers demonstrate a higher functions and enhancing oxidative
However, fiber type alone did not aerobic (oxidative) capacity and a lower capacity through stimulation of
anaerobic (glycolytic) potential than the
determine the performances of the mitochondrial biogenesis (Wu et al.
lighter stained FT fibers. Shorter’s muscle
elite athletes. For example, two athletes contains approximately 80% ST fibers. 2002).
with similar best times for the 42.2 km Reproduced with kind permission from PGC1-α, a transcriptional coactivator
marathon distance (approximately David L. Costill and William J. Fink. of nuclear receptors important
2 hr 18 min) had 50% versus 98% to the regulation of a number of
ST muscle fibers. Subsequent work glucose uptake and metabolism. A mitochondrial genes involved in
(Foster et al. 1978) revealed that shift in fiber distribution from ST to oxidative metabolism, directly interacts
endurance running performance FT fibers gives rise to altered activities with MEF2 to synergistically activate
was better related to an athlete’s of key oxidative and glycolytic enzymes selective ST muscle genes and also
maximal O2 uptake (VO2max; r = −0.84, (Pette and Hofer 1980). Indeed, the serves as a target for calcineurin
−0.87, and −0.88 for 1-, 2-, and 6-mile ratio between glycolytic and oxidative signaling (Lin et al. 2002; Wu et al.
times, respectively). Indeed, while enzyme activities in the skeletal muscle 2001). New data presented in this
an athlete’s muscle fiber type is an of non-insulin-dependent diabetic or issue of PLoS Biology (Wang et al. 2004)
important morphological component obese individuals is related to insulin reveals that a peroxisome proliferator-
and is related to several contractile and resistance (Simoneau et al. 1995; activated receptor δ (PPARδ)-mediated
metabolic properties (see Table 1), Simoneau and Kelley 1997). Similarly, transcriptional pathway is involved in
other physiological factors (e.g., VO2max, with ageing and physical inactivity, two the regulation of the skeletal muscle-
maximal cardiac output, and speed/ other conditions associated with ST-to- fiber phenotype. Mice that harbor
power output at the lactate threshold) FT fiber-type transformation, oxidative an activated form of PPARδ display
are more likely to determine the upper capacity and insulin sensitivity, are an “endurance” phenotype, with a
limits of endurance capacity (Coyle diminished (Papa 1996). coordinated increase in oxidative
1995; Hawley and Stepto 2001). enzymes and mitochondrial biogenesis
Genes That Define Skeletal Muscle and an increased proportion of ST
Do Alterations in Skeletal Muscle Phenotype fibers. Thus—through functional
Fiber Type Contribute to Metabolic Skeletal muscle fiber-type phenotype genomics—calcineurin, calmodulin-
Disease? is regulated by several independent dependent kinase, PGC-1α, and
The close coupling between signaling pathways (Figure 3). These activated PPARδ form the basis of a
muscle fiber type and associated include pathways involved with signaling network that controls skeletal
morphological, metabolic, and the Ras/mitogen-activated protein muscle fiber-type transformation and
functional properties is not confined kinase (MAPK) (Murgia et al. 2000), metabolic profiles that protect against
to athletic ability. Insulin sensitivity calcineurin (Chin et al. 1998; Naya insulin resistance and obesity.
also correlates with the proportion et al. 2000), calcium/calmodulin- The transition from aerobic to
of ST oxidative fibers (Lillioja et al. dependent protein kinase IV (Wu et al. anaerobic metabolism during intense
1987). Specifically, insulin-stimulated 2002), and the peroxisome proliferator work requires that several systems are
glucose transport is greater in skeletal γ coactivator 1 (PGC-1) (Lin et al. rapidly activated to ensure a constant
muscle enriched with ST muscle 2002). The Ras/MAPK signaling supply of ATP for the working muscles.
fibers (Henriksen et al. 1990; Song et pathway links the motor neurons These include a switch from fat-
al. 1999; Daugaard et al. 2000), thus and signaling systems, coupling based to carbohydrate-based fuels,
priming ST muscle for accelerated excitation and transcription regulation a redistribution of blood flow from

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