J Appl Physiol 103: 1536–1542, 2007.
First published August 9, 2007; doi:10.1152/japplphysiol.00575.2007.
PGC-1␤ is downregulated by training in human skeletal muscle: no effect
of training twice every second day vs. once daily on expression of the
PGC-1 family
Ole Hartvig Mortensen,1,2 Peter Plomgaard,1,2 Christian P. Fischer,1,2 Anne K. Hansen,1,2
Henriette Pilegaard,2,3 and Bente Klarlund Pedersen1,2
1
Centre of Inflammation and Metabolism at Department of Infectious Diseases and 2Copenhagen Muscle Research Centre,
Rigshospitalet, and 3Centre of Inflammation and Metabolism, Institute of Molecular Biology and Physiology, August Krogh
Institute, University of Copenhagen, Copenhagen, Denmark
Submitted 28 May 2007; accepted in final form 6 August 2007
REGULAR EXERCISE HAS BEEN shown to be successful as a treatment for a variety of disorders and diseases, including Type 2
diabetes (26). The exact molecular pathways responsible for
these effects have, however, remained elusive. Our laboratory
has previously shown a difference in the outcome of endurance
training employing different training protocols on separate
legs, because an improved adaptation to training occurred in
the leg training twice daily every second day vs. the leg
training once daily (12).
The peroxisome proliferator-activated receptor-␥ coactivator-1; (PGC-1) family of transcriptional coactivators comprises
PGC-1␣, PGC-1␤, and PGC-1 related coactivator (PRC) (4,
20, 29). They have recently emerged as important players in
the regulation of cellular and systemic metabolism, with emphasis on mitochondrial oxidative metabolism and maintenance of glucose, lipid and energy homeostasis (8, 19). Both
PGC-1␣ and PRC have previously been shown to be upregulated in skeletal muscle by acute exercise (6, 27, 31, 35),
whereas PGC-1␤ was unaffected by acute exercise (23).
PGC-1␣ has furthermore been shown to be upregulated in
skeletal muscle by long-term endurance training (11, 16, 30,
32, 34) and downregulated by inactivity (37) or denervation
(14), although its upregulation by training is not consistent in
all cases (27, 38), which may be due to differences in training
protocols and biopsy sample timings. The involvement of the
PGC-1 family in regulation of skeletal muscle metabolism and
fiber type composition has furthermore been corroborated by
overexpression of PGC-1␣ in transgenic mice (21), as well as
in cell culture studies (24), where overexpression of PGC-1␣
induced a phenotype shifted toward an oxidative fiber type.
Recently, it was shown that overexpression of PGC-1␤ in
skeletal muscle cell culture selectively induced the expression
of myosin heavy chain IIA (MHC IIA) mRNA compared with
PGC-1␣ overexpression (24), showing that more than just one
member of the PGC-1 family is involved in skeletal muscle
fiber-type control and thus possibly training adaptation. The
possible involvement of all the PGC-1 family members in
skeletal muscle fiber-type control is also evidenced by the
observations that the PGC-1 family is expressed at different
levels in different skeletal muscle fibers in rodents, with
PGC-1␣ being more highly expressed in skeletal muscle consisting mainly of type 1 fibers (14, 21) and PGC-1␤ being
expressed more highly in skeletal muscle consisting mainly of
type 2 fibers (14). Loss of PGC-1␣ further implicates PGC-1␣
in skeletal muscle adaptation as PGC-1␣ knockout mice exhibit impaired skeletal muscle strength, reduced exercise capacity, and decreased fatigue resistance (18). PGC-1␣ has been
implicated in control of pyruvate dehydrogenase kinase 4,
suggesting a direct link between levels of PGC-1␣ and glyco-
Address for reprint requests and other correspondence: O. H. Mortensen,
Centre of Inflammation and Metabolism, Rigshospitalet 7641, Blegdamsvej 9,
DK-2100 Copenhagen, Denmark (e-mail: [email protected]).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
peroxisome proliferator-activated receptor-␥ coactivator-1; peroxisome proliferator-activated receptor-␥ coactivator-1␤; peroxisome
proliferator-activated receptor-␥ coactivator-1-related cofactor; adaptation; glycogen
1536
8750-7587/07 $8.00 Copyright © 2007 the American Physiological Society
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Mortensen OH, Plomgaard P, Fischer CP, Hansen AK,
Pilegaard H, Pedersen BK. PGC-1␤ is downregulated by training
in human skeletal muscle: no effect of training twice every second
day vs. once daily on expression of the PGC-1 family. J Appl
Physiol 103: 1536–1542, 2007. First published August 9, 2007;
doi:10.1152/japplphysiol.00575.2007.—We hypothesized that the
peroxisome proliferator-activated receptor-␥ coactivator-1 (PGC-1)
family of transcriptional coactivators (PGC-1␣, PGC-1␤, and PRC) is
differentially regulated by training once daily vs. training twice daily
every second day and that this difference might be observed in the
acute response to endurance exercise. Furthermore, we hypothesized
that expression levels of the PGC-1 family differ with muscular
fiber-type composition. Thus, before and after 10 wk of knee extensor
endurance training, training one leg once daily and the other leg twice
daily every second day, keeping the total amount of training for the
legs equal, skeletal muscle mRNA expression levels of PGC-1␣,
PGC-1␤, and PRC were determined in young healthy men (n ⫽ 7) in
response to 3 h of acute exercise. No significant difference was found
between the two legs, suggesting that regulation of the PGC-1 family
is independent of training protocol. Training decreased PGC-1␤ in
both legs, whereas PGC-1␣ was increased, but not significantly, in the
leg training once daily. PRC did not change with training. Both
PGC-1␣ and PRC were increased by acute exercise both before and
after endurance training, whereas PGC-1␤ did not change. The
mRNA levels of the PGC-1 family were examined in different types
of human skeletal muscle (triceps, soleus, and vastus lateralis; n ⫽ 7).
Only the expression level of PGC-1␤ differed and correlated inversely
with percentage of type I fibers. In conclusion, there was no difference
between training protocols on the acute exercise and training response
of the PGC-1 family. However, training caused a decrease in PGC-1␤
mRNA levels.
EXERCISE AND TRAINING RESPONSE OF THE PGC-1 FAMILY
MATERIALS AND METHODS
Study 1: training study. Seven healthy untrained young men [age
26 ⫾ 1 yr (mean ⫾ SE), body mass 86 ⫾ 9 kg, and body mass index
(BMI) 26.4 ⫾ 1.8 kg/m2] were recruited to the study. All volunteers
underwent a medical examination and a standard set of blood tests.
Purpose and possible risks of the study were explained to the participants before written consents were obtained. The study protocol was
approved by the local Ethical Committee of Copenhagen and Frederiksberg Communities and was performed in accordance with the
Declaration of Helsinki.
The study was carried out as previously described (12). Briefly,
Pmax during dynamic one-legged knee extensor exercise was determined both before (pretraining) and after (posttraining) 10 wk of
endurance training for all participants as described below. The participants trained each leg for 1 h five times a week using dynamic oneJ Appl Physiol • VOL
or two-legged knee extensor exercise, training each leg after different
schedules (12). By randomization, all subjects trained one leg twice
daily every second day while the other leg was trained once daily. In
total, this yielded 50 days of training once daily for one leg and 25
days of training twice daily every second day for the other leg, thus
making the total amount of training per leg equal. The initial workload
during the 10 wk of exercise training was 75% of Pmax with a 5–10%
increase in workload every 2 wk depending on the progress of each
participant. Acute exercise bouts were carried out as described below
both before and after 10 wk of training, with the participants being
instructed to refrain from exercise 48 h before the test.
Exercise performance tests. Pmax was determined during dynamic
one-legged knee extensor exercise with the use of a modified ergometer, as described earlier (3). Each leg was tested individually to
exclude possible differences between the dominant and nondominant
leg. The Pmax test consisted of a short warm-up session with 60 knee
extensions/min at 30 W. This was followed up by an incremental
increase of the workload by 10 W every 2 min until volitional
exhaustion. The highest workload that was maintained for at least 1
min was defined as Pmax. In addition, each Pmax test was followed by
a second test using a workload corresponding to 90% of Pmax to
determine Texh during submaximal exercise. The last set of performance tests were carried out ⬎48 h after the last training session.
Acute exercise experiment. After completion of the tests for determination of Pmax and Texh, the participants performed an acute
exercise experiment using the dynamic knee extensor exercise model
(3). The acute exercise experiment was performed before as well as
after the 10 wk of endurance training. On the experimental days,
participants reported to the laboratory at 0800 after an overnight fast.
Furthermore, the participants were instructed to refrain from exercise
for at least 48 h before the experiment, and, accordingly, the acute
exercise experiment was performed ⬎48 h after the last set of
performance tests. The exercise bout consisted of 3 h of dynamic
two-legged knee extensor exercise at 60 extensions/min, with the
workload per leg set to 50% of the individual and actual Pmax. After
the exercise bout, the subjects rested in the supine position for a 2-h
recovery period. Water was consumed ad libitum, whereas food was
not permitted until the end of the recovery period. Muscle biopsies
were taken from the vastus lateralis before exercise start, immediately
after exercise, and 2 h postexercise. The biopsies used were the same
as in a previously published study (12).
Study 2: fiber-type study. Seven healthy untrained young men [age
26 ⫾ 1 yr (mean ⫾ SE), body mass 84 ⫾ 3 kg, and BMI 24.7 ⫾ 0.1
kg/m2] were recruited to the study. All volunteers underwent a
medical examination and a standard set of blood tests. Purpose and
possible risks of the study were explained to the participants before
written consents were obtained. The study protocol was approved by
the local Ethical Committee of Copenhagen and Frederiksberg Communities and was performed in accordance with the Declaration of
Helsinki. The study was carried out as previously described (28).
Briefly, the subjects were instructed not to perform any vigorous
exercise 24 h before the experiment and to report at the laboratory
after an overnight fast. Biopsies were obtained from three different
muscle groups: triceps brachii caput medialis (triceps), triceps surae
pars soleus (soleus), and quadriceps pars vastus lateralis (vastus) as
described below. The biopsies used were the same as in a previously
published study (28).
Muscle biopsies. Muscle biopsies were obtained using the Bergström percutaneous needle method with suction (7). In study 1, muscle
biopsy samples were obtained using the Bergström percutaneous
needle method with suction before and after 10 wk of training from
the quadriceps pars vastus lateralis muscle of both legs. In study 2,
biopsies were obtained from three different muscle groups: triceps,
soleus, and vastus by using a Bergström biopsy needle. Before each
biopsy, local anesthesia (lidocaine, 20 mg/ml; SAD) was applied to
the skin and fascia superficial of the biopsy site. In the training study,
a new incision site was made for each biopsy, and all incision sites
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gen (5, 22, 40) and overexpression of PGC-1␣ has been shown
to increase the levels of glycogen in skeletal muscle cell culture
(24). It has, however, not been examined whether glycogen
levels affect the expression of the PGC-1 family, but several
reports suggest a link between substrate availability and
PGC-1␣ expression, mediated by AMP-activated protein kinase (AMPK), because AMPK activation has been shown to be
associated with an increase in PGC-1␣ expression (17, 33).
AMPK has, however, been shown to be dispensable for exercise induction of PGC-1␣ (13). All members of the PGC-1
family have been shown to upregulate mitochondrial biogenesis as well as to regulate a large variety of mitochondriaspecific genes (10).
Our laboratory has previously reported on a study where
subjects performed one-legged or two-legged knee extensor
endurance training for 10 wk following a protocol where one
leg trained twice daily every second day and the other trained
once daily (12); thus training one leg markedly more in a
low-glycogen state than the other, with both legs receiving the
same total amount of training over the 10-wk study period.
This resulted in a marked similar increase in maximal power
output (Pmax) in both legs, whereas the leg training twice daily
every second day ended up with twice as long a time to exhaustion
(Texh) compared with the leg training once daily (12). Furthermore, there was a similar increase in 3-hydroxyacyl-CoA
dehydrogenase (HAD) enzyme activity in the two legs,
whereas citrate synthase (CS) increased markedly more in the
leg training twice daily every second day, suggesting that
training twice daily every second day induced a more oxidative
skeletal muscle phenotype.
The rationale for this study is that the superior increase in
oxidative capacity and Texh, seen when training twice daily
every second day compared with training once daily, might be
explained by differences in factors known to be majorly involved in the control of skeletal muscle oxidative metabolism
and training adaptation. Thus we hypothesized that changes in
the expression levels of the PGC-1 family of transcriptional
coactivators might be the underlying cause of the difference
seen between the two differentially trained legs and that the
difference in training protocol would differentially regulate the
PGC-1 family of transcriptional coactivators. We hypothesized
that this effect might be apparent in the acute response to
exercise of legs trained either once daily or twice daily every
second day. Furthermore, we hypothesized that muscles with
different fiber-type compositions differ in their expression
levels of these coactivators.
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EXERCISE AND TRAINING RESPONSE OF THE PGC-1 FAMILY
RESULTS
Effect of training on the acute exercise response of the
PGC-1 family mRNA levels. The effect of training and training
protocol on the acute exercise response of the PGC-1 family
was assessed by measuring the mRNA levels before, directly
after, or 2 h after 3 h of dynamic knee extensor exercise at the
same relative intensity before and after training (Fig. 1).
Overall there was no difference between training once daily
vs. training twice daily every second day in terms of the
response of the PGC-1 family to acute exercise. Nor was there
a difference between the resting levels of the PGC-1 family in
the two legs.
The resting levels of PGC-1␣ mRNA increased by ⬃50%
with training but only significantly so when training twice daily
every second day. Surprisingly, the resting levels of PGC-1␤
mRNA significantly decreased by ⬃35% regardless of training
protocol. Training had no effect on the resting mRNA levels
of PRC.
PGC-1␣ mRNA levels increased in response to acute exercise, showing a maximal increase of ⬃10-fold after training
and 5-fold before training. The exercise-induced increase in
J Appl Physiol • VOL
PGC-1␣ was more pronounced 2 h postexercise after training
than before training, when training twice daily every second
day (P ⫽ 0.043) but not when training once daily (P ⫽ 0.074).
Acute exercise had no effect on PGC-1␤ mRNA levels,
whereas PRC mRNA levels increased following acute exercise
without effect of training.
PGC-1 family mRNA levels in different skeletal muscle
types. The expression levels of PGC-1␣, PGC-1␤, and PRC
were also determined in three different skeletal muscle types,
triceps, soleus, and vastus, in young healthy men (Fig. 2).
Soleus consisted of 68 – 83% (range) type I fibers, vastus
lateralis of 40 –56% type I fibers, and triceps of 20 –33% type
I fibers (28). Only PGC-1␤ was differentially expressed in
human skeletal muscle, with triceps having approximately
twice the mRNA expression level compared with vastus and
soleus. Accordingly, we found a highly significant negative
correlation between PGC-1␤ mRNA levels and percentage of
type I fibers (P ⫽ 0.0002), whereas there was no correlation
between PRC and percent type I fibers (Fig. 2). As previously
reported, we did not find any correlation between PGC-1␣ and
percent type 1 fibers (28).
DISCUSSION
The present study demonstrated that the muscular expression
of all members of the PGC-1 family is regulated either by acute
exercise or by training. The main novel findings of this study
were that 1) Training once daily vs. training twice daily every
second day makes no difference in terms of the effect caused
by endurance training on the mRNA expression of the PGC-1
family of transcriptional coactivators, 2) PGC-1␤ mRNA in
skeletal muscle is downregulated by endurance training, and
3) PGC-1␤ mRNA is preferentially expressed in triceps and
correlates negatively with percentage of type I fibers.
Exercise and the PGC-1 family of transcriptional coactivators. The increase of PGC-1␣ in skeletal muscle by acute
exercise was in accordance with previous studies in humans
(25, 27, 31, 39), rats (6, 9, 14, 36), and mice (1, 2, 13). Other
studies have previously found an effect of endurance training
on resting PGC-1␣ levels in humans (16, 30, 32) and rats (9,
11, 14, 34). However, a previous study by Pilegaard et al. (27),
employing a protocol similar to the training once daily leg in
this study, found no significant increase in resting PGC-1␣
mRNA levels following 4 wk of training. The present study
suggests that PGC-1␣ mRNA might be more consistently
increased by training when training two times a day; however,
when comparing training once daily with training twice daily
every second day, no significant difference was found. Generally, training adaptation is associated with an increase in
muscle glycogen content, and training twice daily every second
day induced a significant increase in muscle glycogen content
posttraining, whereas the increase in glycogen content was not
statistically significant for training once daily (12). Furthermore, overexpression of PGC-1␣ in skeletal muscle cell culture increases glycogen levels in vitro (24). Despite these
observations, we saw no overt difference in the PGC-1␣
mRNA levels when training once daily vs. training twice daily
every second day, which is reminiscent of the finding that there
was no difference between the glycogen levels in both legs at
rest following the 10 wk of training. Interestingly, only the leg
that showed a statistical significant increase in PGC-1␣ mRNA
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were at minimum 3 cm apart. Visible connective tissue and blood
contamination were removed before the biopsies were frozen in liquid
nitrogen and subsequently stored at ⫺80°C until further analysis.
The biopsies used were the same as in previously published studies
(12, 28).
Real-time RT-PCR. Total RNA was extracted from the muscle
tissue with the use of TRIzol according to the manufacturer’s instructions (Invitrogen, Grand Island, NY). The resulting RNA pellet was
dissolved in diethylpyrocarbonate-treated water. Reverse transcription
(RT) reactions were performed using random hexamers on 2 ␮g RNA
using an RT kit (Applied Biosystems, Foster City, CA) in a reaction
volume of 100 ␮l. The resulting cDNA product was stored at ⫺20°C
until further analysis. Primers and probes for PGC-1␣ were designed
(Primer Express version 1.0, Applied Biosystems) from the gene
sequences for human PGC-1␣ as described previously (27); forward
primer 5⬘-CAAGCCAAACCAACAACTTTATCTCT-3⬘, reverse
primer 5⬘-CACACTTAAGGTGCGTTCAATAGTC-3⬘, and TaqMan
fluorescent probe 5⬘-FAM-AGTCACCAAATGACCCCAAGGGTTCC-TAMRA-3⬘. PGC-1␤, PRC, ␤-actin, and 18S rRNA were amplified using predeveloped assay reagents (Applied Biosystems),
Hs00370186_m1 (PGC-1␤), Hs00209379_m1 (PRC). The mRNA
levels of PGC-1␣, PGC-1␤, and PRC as well as the mRNA levels of
the endogenous controls, 18S rRNA and ␤-actin, were determined by
real-time RT-PCR using an ABI PRISM 7900 sequence detector
(Applied Biosystems). 18S rRNA was used to normalize mRNA
expression values in the training study, and ␤-actin was used to
normalize mRNA expression values in the fiber-type study. Comparable results were obtained if values in the training study were
normalized to GAPDH instead of 18S (data not shown).
Statistics. Data were log transformed to obtain normal distribution.
Accordingly, results are presented as geometric means ⫾ SE. All
statistics were performed on log-transformed values using SAS 9.1.2
(SAS Institute). The training study was analyzed using mixed-model
statistics to detect the effect of training protocol after which the study
was split up, and, using mixed model statistics, each training protocol
was examined individually with regard to training and time, followed
by post hoc t-tests with Bonferroni correction to identify differences
between groups at specific time points. A one-way ANOVA was used
to detect differences between the three muscle groups in the fiber type
study, followed by post hoc t-test with Bonferroni correction.
Correlation analyses were done using Pearson correlation analysis.
A P value ⬍0.05 was considered significant.
EXERCISE AND TRAINING RESPONSE OF THE PGC-1 FAMILY
1539
also showed a significant increase in glycogen content following training.
In the present study, the PGC-1␤ mRNA content was downregulated by endurance training, but no changes were observed
at the investigated time points following acute exercise. The
latter finding is in accordance with a few previous studies
showing no effect of acute exercise (14, 23). In a crosssectional study, others have found a higher level of PGC-1␤ in
trained than in untrained or spinal cord-injured humans (15);
however, the difference in expression levels might have taken
years to develop. Thus it appears that the kinetics of changing
PGC-1␤ expression by exercise in skeletal muscle is long term,
which might be reminiscent of training adaptation and that
perhaps the level of PGC-1␤ changes as training adaptation
progresses.
PRC, the last PGC-1 family member, has previously been
shown to be upregulated by acute endurance exercise (31).
Here we show yet another pattern of regulation of a PGC-1
family member by exercise, because PRC was only regulated
by acute endurance exercise and not by long-term endurance
training. This finding suggests that PRC may play a role during
J Appl Physiol • VOL
exercise or in the recovery phase, but that its expression level
does not reflect training adaptation to endurance exercise
because no change in PRC mRNA levels was observed comparing pre- and posttraining levels at rest.
We previously found that as an effect of training the increase
in maximal workload was identical for the two legs; however,
time to exhaustion at 90% of actual maximal workload before
and after 10 wk of training was much more increased when
training twice daily every second day compared with training
once a day. This could not be explained by a difference in
glycogen content, because the time to exhaustion tests were
carried out at a relative high intensity, which did not allow the
volunteers to exercise for more than a maximum of 25 min,
ensuring that glycogen was not a limiting factor. In light of the
findings in this study, it seems that differences in the expression levels of the PGC-1 family members are not a plausible
explanation for the difference in Texh seen when training twice
daily every second day compared with training once daily (12).
Both PGC-1␣ and PGC-1␤ are known to control expression
of CS (24), as well as control mitochondrial ␤-oxidation (19).
In an earlier study, our laboratory found both CS and HAD to
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Fig. 1. Peroxisome proliferator-activated receptor-␥
coactivator-1 ␣ (PGC-1␣), peroxisome proliferatoractivated receptor-␥ coactivator-1␤ (PGC-1␤), and
peroxisome proliferator-activated receptor-␥ coactivator-1-related cofactor (PRC) mRNA levels in muscle biopsies before (pre), immediately after 3 h of
endurance exercise (post), and 2 h after 3 h of endurance exercise (2h post) in the leg trained either once
daily (left) or in the leg trained twice daily every
second day (right) for 10 wk. Data are presented as
geometric means ⫾ SE for 7 subjects. Open bars,
results from the 3-h acute exercise experiment before
endurance exercise training (pretraining); solid bars,
results from the 3-h acute exercise experiment after
the training period (posttraining). NS, not significant.
#P ⬍ 0.05, different from 0 h. †P ⬍ 0.01, different
from 0 h. ‡P ⬍ 0.001, different from 0 h. $P ⬍ 0.05,
difference between pre- and posttraining.
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EXERCISE AND TRAINING RESPONSE OF THE PGC-1 FAMILY
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Fig. 2. PGC-1␣, PGC-1␤, and PRC mRNA
levels in skeletal muscle biopsies taken from
either triceps brachii caput medialis (triceps),
triceps surae pars soleus (soleus), and quadriceps pars vastus lateralis (vastus). Data are
presented as geometric means ⫾ SE (left) or as
correlations between PGC-1␣, PGC-1␤, and
PRC mRNA levels and type I fiber composition (right) for 7 subjects. Biopsies from the
same subjects are connected, and the muscle
type is marked as follows: triceps (■), vastus
(Œ), and soleus (䊐). Bold line, result of the
linear regression. †P ⬍ 0.01 different from
triceps. ‡P ⬍ 0.001, different from triceps.
increase following training, with the leg training twice daily
every second day having a significantly higher CS increase
than the leg training once daily (12). The lack of a similar
pattern in the expression levels of PGC-1␣ and PGC-1␤
following the training period again suggests that changes in the
expression level of the PGC-1 family are not a plausible
explanation for the difference seen between the two training
protocols. Unfortunately, in this study, we can not exclude the
possibility that training in a low-glycogen state, e.g., the
second bout of training of the leg training twice a day every
second day, gives rise to a temporarily different expression
pattern of the PGC-1 family members (12). However, we found
no evidence of this in the resting state or in the acute exercise
experiments performed after the 10 wk of training.
Skeletal muscle phenotype and PGC-1 family expression. A
few studies have shown differential expression of PGC-1␣
mRNA with either skeletal muscle fiber type or skeletal muscle
type. In humans, PGC-1␣ protein content is higher in type
MHC IIA than in type MHC I and MHC IIX fibers (30). In
rodents, huge differences in PGC-1␣ mRNA levels are seen
between muscle types with PGC-1␣ mRNA levels being up to
J Appl Physiol • VOL
five times higher in soleus (primarily type 1 fibers) than in any
other muscle types (14, 21). Our laboratory has previously
shown that there is no difference in PGC-1␣ mRNA levels in
humans between the three skeletal muscle types examined in
this study (28), which we also find here.
PGC-1␤ has been demonstrated to have huge differences in
mRNA expression levels in different rodent muscle types, with
PGC-1␤ mRNA levels being up to four times higher in extensor digitorum longus (primarily type 2 fibers) than in soleus
and gastrocnemius (14). Our finding that PGC-1␤ mRNA
levels are higher in triceps (primarily type 2 fibers) than in both
vastus (intermediate with respect to type 1 and 2 fibers) and
soleus (primarily type 1 fibers) suggests that similar differences
exists in human skeletal muscle.
Using 18S as the reference gene, Koves et al. (14) showed a
remarkable difference in PGC-1␣ expression levels in different
fiber types from the same muscle in rats. Our laboratory has
previously shown that 18S is differentially expressed in the
different muscle types in humans (28), whereas ␤-actin is more
stable and suitable as an endogenous control in the present
study. The inconsistency between Koves et al. (14) and our
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EXERCISE AND TRAINING RESPONSE OF THE PGC-1 FAMILY
studies may not only rely on species difference but may also be
related to the chosen reference gene.
Conclusion. This is the first complete assessment of the
changes in mRNA levels of the PGC-1 family of transcriptional coactivators induced by either acute exercise or endurance training in humans showing a remarkably different regulation of all three family members by endurance exercise or
training. Furthermore, we here show for the first time a possible involvement of PGC-1␤ in the adaptive response of skeletal
muscle to endurance training. Finally, we showed that there
was no difference between training protocols on the acute
exercise and training response of the PGC-1 family and that
training caused a decrease in PGC-1␤ mRNA levels at rest.
ACKNOWLEDGMENTS
15.
16.
17.
18.
The authors are grateful for the excellent technical assistance of Hanne
Villumsen, Ruth Rousing, and Bettina Mentz.
GRANTS
19.
20.
21.
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This study was funded by the Centre of Inflammation and Metabolism
(supported by Danish National Research Foundation Grant DG 02-512-555);
the Copenhagen Muscle Research Centre (supported by grants from The
University of Copenhagen, the Faculties of Science and of Health Sciences at
this university); the Copenhagen Hospital Corporation, Danish National Research Foundation Grant 504-14; and the Commission of the European Communities (contract no. LSHM-CT-2004-005272 EXGENESIS).
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