PGC-1β 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

2007 ◽  
Vol 103 (5) ◽  
pp. 1536-1542 ◽  
Author(s):  
Ole Hartvig Mortensen ◽  
Peter Plomgaard ◽  
Christian P. Fischer ◽  
Anne K. Hansen ◽  
Henriette Pilegaard ◽  
...  

We hypothesized that the peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) family of transcriptional coactivators (PGC-1α, PGC-1β, 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-1α, PGC-1β, 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-1β in both legs, whereas PGC-1α was increased, but not significantly, in the leg training once daily. PRC did not change with training. Both PGC-1α and PRC were increased by acute exercise both before and after endurance training, whereas PGC-1β 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-1β 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-1β mRNA levels.

1996 ◽  
Vol 80 (2) ◽  
pp. 699-705 ◽  
Author(s):  
T. Tsakiridis ◽  
P. P. Wong ◽  
Z. Liu ◽  
C. D. Rodgers ◽  
M. Vranic ◽  
...  

Muscle fibers adapt to ionic challenges of exercise by increasing the plasma membrane Na+-K+ pump activity. Chronic exercise training has been shown to increase the total amount of Na+-K+ pumps present in skeletal muscle. However, the mechanism of adaptation of the Na+-K+ pump to an acute bout of exercise has not been determined, and it is not known whether it involves alterations in the content of plasma membrane pump subunits. Here we examine the effect of 1 h of treadmill running (20 m/min, 10% grade) on the subcellular distribution and expression of Na+-K+ pump subunits in rat skeletal muscles. Red type I and IIa (red-I/IIa) and white type IIa and IIb (white-IIa/IIb) hindlimb muscles from resting and exercised female Sprague-Dawley rats were removed for subcellular fractionation. By homogenization and gradient centrifugation, crude membranes and purified plasma membranes were isolated and subjected to gel electrophoresis and immunoblotting by using pump subunit-specific antibodies. Furthermore, mRNA was isolated from specific red type I (red-I) and white type IIb (white-IIb) muscles and subjected to Northern blotting by using subunit-specific probes. In both red-I/IIa and white-IIa/IIb muscles, exercise significantly raised the plasma membrane content of the alpha1-subunit of the pump by 64 +/- 24 and 55 +/- 22%, respectively (P < 0.05), and elevated the alpha2-polypeptide by 43 +/- 22 and 94 +/- 39%, respectively (P < 0.05). No significant effect of exercise could be detected on the amount of these subunits in an internal membrane fraction or in total membranes. In addition, exercise significantly increased the alpha1-subunit mRNA in red-I muscle (by 50 +/- 7%; P < 0.05) and the beta2-subunit mRNA in white-IIb muscles (by 64 +/- 19%; P < 0.01), but the alpha2- and beta1-mRNA levels were unaffected in this time period. We conclude that increased presence of alpha1- and alpha2-polypeptides at the plasma membrane and subsequent elevation of the alpha1- and beta2-subunit mRNAs may be mechanisms by which acute exercise regulates the Na+-K+ pump of skeletal muscle.


2004 ◽  
Vol 97 (6) ◽  
pp. 2148-2153 ◽  
Author(s):  
Paul J. LeBlanc ◽  
Krista R. Howarth ◽  
Martin J. Gibala ◽  
George J. F. Heigenhauser

This is the first study to examine the effects of endurance training on the activation state of glycogen phosphorylase (Phos) and pyruvate dehydrogenase (PDH) in human skeletal muscle during exercise. We hypothesized that 7 wk of endurance training (Tr) would result in a posttransformationally regulated decrease in flux through Phos and an attenuated activation of PDH during exercise due to alterations in key allosteric modulators of these important enzymes. Eight healthy men (22 ± 1 yr) cycled to exhaustion at the same absolute workload (206 ± 5 W; ∼80% of initial maximal oxygen uptake) before and after Tr. Muscle biopsies (vastus lateralis) were obtained at rest and after 5 and 15 min of exercise. Fifteen minutes of exercise post-Tr resulted in an attenuated activation of PDH (pre-Tr: 3.75 ± 0.48 vs. post-Tr: 2.65 ± 0.38 mmol·min−1·kg wet wt−1), possibly due in part to lower pyruvate content (pre-Tr: 0.94 ± 0.14 vs. post-Tr: 0.46 ± 0.03 mmol/kg dry wt). The decreased pyruvate availability during exercise post-Tr may be due to a decreased muscle glycogenolytic rate (pre-Tr: 13.22 ± 1.01 vs. post-Tr: 7.36 ± 1.26 mmol·min−1·kg dry wt−1). Decreased glycogenolysis was likely mediated, in part, by posttransformational regulation of Phos, as evidenced by smaller net increases in calculated muscle free ADP (pre-Tr: 111 ± 16 vs. post-Tr: 84 ± 10 μmol/kg dry wt) and Pi (pre-Tr: 57.1 ± 7.9 vs. post-Tr: 28.6 ± 5.6 mmol/kg dry wt). We have demonstrated for the first time that several signals act to coordinately regulate Phos and PDH, and thus carbohydrate metabolism, in human skeletal muscle after 7 wk of endurance training.


2004 ◽  
Vol 287 (2) ◽  
pp. R397-R402 ◽  
Author(s):  
Lotte Jensen ◽  
Henriette Pilegaard ◽  
P. Darrell Neufer ◽  
Ylva Hellsten

The present study investigated the effect of an acute exercise bout on the mRNA response of vascular endothelial growth factor (VEGF) splice variants in untrained and trained human skeletal muscle. Seven habitually active young men performed one-legged knee-extensor exercise training at an intensity corresponding to ∼70% of the maximal workload in an incremental test five times/week for 4 wk. Biopsies were obtained from the vastus lateralis muscle of the trained and untrained leg 40 h after the last training session. The subjects then performed 3 h of two-legged knee-extensor exercise, and biopsies were obtained from both legs after 0, 2, 6, and 24 h of recovery. Real-time PCR was used to examine the expression of VEGF mRNA containing exon 1 and 2 (all VEGF isoforms), exon 6 or exon 7, and VEGF165mRNA. Acute exercise induced an increase ( P < 0.05) in total VEGF mRNA levels as well as VEGF165and VEGF splice variants containing exon 7 at 0, 2, and 6 h of recovery. The increase in VEGF mRNA was higher in the untrained than in the trained leg ( P < 0.05). The results suggest that in human skeletal muscle, acute exercise increases total VEGF mRNA, an increase that appears to be explained mainly by an increase in VEGF165mRNA. Furthermore, 4 wk of training attenuated the exercise-induced response in skeletal muscle VEGF165mRNA.


2000 ◽  
Vol 279 (2) ◽  
pp. H772-H778 ◽  
Author(s):  
R. S. Richardson ◽  
H. Wagner ◽  
S. R. D. Mudaliar ◽  
E. Saucedo ◽  
R. Henry ◽  
...  

Angiogenesis is a component of the multifactoral adaptation to exercise training, and vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation. However, there is limited evidence supporting the role of VEGF in the exercise training response. Thus we studied mRNA levels of VEGF, using quantitative Northern analysis, in untrained and trained human skeletal muscle at rest and after a single bout of exercise. Single leg knee-extension provided the acute exercise stimulus and the training modality. Four biopsies were collected from the vastus lateralis muscle at rest in the untrained and trained conditions before and after exercise. Training resulted in a 35% increase in muscle oxygen consumption and an 18% increase in number of capillaries per muscle fiber. At rest, VEGF/18S mRNA levels were similar before (0.38 ± 0.04) and after (1.2 ± 0.4) training. When muscle was untrained, acute exercise greatly elevated VEGF/18S mRNA levels (16.9 ± 6.7). The VEGF/18S mRNA response to acute exercise in the trained state was markedly attenuated (5.4 ± 1.3). These data support the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis and appears to be subject to a negative feedback mechanism as exercise adaptations occur.


2009 ◽  
Vol 107 (1) ◽  
pp. 283-289 ◽  
Author(s):  
Robert S. Lee-Young ◽  
Benedict J. Canny ◽  
Damian E. Myers ◽  
Glenn K. McConell

AMP-activated protein kinase (AMPK) has been extensively studied in whole muscle biopsy samples of humans, yet the fiber type-specific expression and/or activation of AMPK is unknown. We examined basal and exercise AMPK-α Thr172 phosphorylation and AMPK subunit expression (α1, α2, and γ3) in type I, IIa, and IIx fibers of human skeletal muscle before and after 10 days of exercise training. Before training basal AMPK phosphorylation was greatest in type IIa fibers ( P < 0.05 vs. type I and IIx), while an acute bout of exercise increased AMPK phosphorylation in all fibers ( P < 0.05), with the greatest increase occurring in type IIx fibers. Exercise training significantly increased basal AMPK phosphorylation in all fibers, and the exercise-induced increases were uniformly suppressed compared with pretraining exercise. Expression of AMPK-α1 and -α2 was similar between fibers and was not altered by exercise training. However, AMPK-γ3 was differentially expressed in skeletal muscle fibers (type IIx > type IIa > type I), irrespective of training status. Thus skeletal muscle AMPK phosphorylation and AMPK expression are fiber type specific in humans in the basal state, as well as during exercise. Our findings reveal fiber type-specific differences that have been masked in previous studies examining mixed muscle samples.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Chunlei Miao ◽  
Lulu Zhou ◽  
Lufeng Tian ◽  
Yingjie Zhang ◽  
Wei Zhang ◽  
...  

Expedited bone tissue engineering employs the biological stimuli to harness the intrinsic regenerative potential of skeletal muscle to trigger the reparative process in situ to improve or replace biological functions. When genetically modified with adenovirus mediated BMP2 gene transfer, muscle biopsies from animals have demonstrated success in regenerating bone within rat bony defects. However, it is uncertain whether the human adult skeletal muscle displays an osteogenic potential in vitro when a suitable biological trigger is applied. In present study, human skeletal muscle cultured in a standard osteogenic medium supplemented with dexamethasone demonstrated significant increase in alkaline phosphatase activity approximately 24-fold over control at 2-week time point. More interestingly, measurement of mRNA levels revealed the dramatic results for osteoblast transcripts of alkaline phosphatase, bone sialoproteins, transcription factor CBFA1, collagen type I, and osteocalcin. Calcified mineral deposits were demonstrated on superficial layers of muscle discs after an extended 8-week osteogenic induction. Taken together, these are the first data supporting human skeletal muscle tissue as a promising potential target for expedited bone regeneration, which of the technologies is a valuable method for tissue repair, being not only effective but also inexpensive and clinically expeditious.


2013 ◽  
Vol 304 (12) ◽  
pp. E1379-E1390 ◽  
Author(s):  
Brynjulf Mortensen ◽  
Janne R. Hingst ◽  
Nicklas Frederiksen ◽  
Rikke W. W. Hansen ◽  
Caroline S. Christiansen ◽  
...  

Subjects with a low birth weight (LBW) display increased risk of developing type 2 diabetes (T2D). We hypothesized that this is associated with defects in muscle adaptations following acute and regular physical activity, evident by impairments in the exercise-induced activation of AMPK signaling. We investigated 21 LBW and 21 normal birth weight (NBW) subjects during 1 h of acute exercise performed at the same relative workload before and after 12 wk of exercise training. Multiple skeletal muscle biopsies were obtained before and after exercise. Protein levels and phosphorylation status were determined by Western blotting. AMPK activities were measured using activity assays. Protein levels of AMPKα1 and -γ1 were significantly increased, whereas AMPKγ3 levels decreased with training independently of group. The LBW group had higher exercise-induced AMPK Thr172 phosphorylation before training and higher exercise-induced ACC2 Ser221 phosphorylation both before and after training compared with NBW. Despite exercise being performed at the same relative intensity (65% of V̇o2peak), the acute exercise response on AMPK Thr172, ACC2 Ser221, AMPKα2β2γ1, and AMPKα2β2γ3 activities, GS activity, and adenine nucleotides as well as hexokinase II mRNA levels were all reduced after exercise training. Increased exercise-induced muscle AMPK activation and ACC2 Ser221 phosphorylation in LBW subjects may indicate a more sensitive AMPK system in this population. Long-term exercise training may reduce the need for AMPK to control energy turnover during exercise. Thus, the remaining γ3-associated AMPK activation by acute exercise after exercise training might be sufficient to maintain cellular energy balance.


1999 ◽  
Vol 86 (6) ◽  
pp. 1828-1832 ◽  
Author(s):  
Joseph A. Houmard ◽  
D. Sean O’Neill ◽  
Donghai Zheng ◽  
Matthew S. Hickey ◽  
G. Lynis Dohm

The purpose of this study was to determine whether hyperinsulinemia alters myosin heavy chain (MHC) gene expression in human skeletal muscle. A biopsy from the vastus lateralis was obtained in young, lean [age 24.6 ± 1.0 (SE) yr, body fat 11.9 ± 1.9%, body mass index 26.1 ± 1.1 kg/m2; n = 10] men before and after 3 h of hyperinsulinemia (hyperinsulinemic-euglycemic clamp). Muscle was analyzed for mRNA of type I, IIa, and IIx MHC isoforms. Hyperinsulinemia (mean of 1,065.7 ± 9.8 pmol/l during minutes 20 to 180) did not change ( P > 0.05) the mRNA concentration of either the type I MHC or type IIA MHC isoforms. In contrast, type IIX MHC mRNA increased ( P < 0.05) with hyperinsulinemia compared with the fasted condition. These data indicate that hyperinsulinemia rapidly increases type IIx MHC mRNA in human skeletal muscle.


2021 ◽  
Author(s):  
Sebastian Gehlert ◽  
Patrick Weinisch ◽  
Werner Römisch-Margl ◽  
Richard T. Jaspers ◽  
Anna Artati ◽  
...  

Abstract Resistance training promotes metabolic health and stimulates muscle hypertrophy, but the precise routes by which resistance exercise (RE) conveys these health benefits is largely unknown. Aim: To investigate how acute RE affects human skeletal muscle metabolism. Methods: We collected vastus lateralis biopsies from six healthy male untrained volunteers at rest, before the first of 13 RE training sessions, and 45 min after the first and last bouts of RE. Biopsies were analysed using untargeted mass spectrometry-based metabolomics. Results: We measured 617 metabolites covering a broad range of metabolic pathways. In the untrained state RE altered 33 metabolites, including increased 3-methylhistidine and 1-carboxylethylvaline, suggesting increased protein breakdown, as well as metabolites linked to ATP (xanthosine) and NAD (N1-methyl-2-pyridone-5-carboxamide) metabolism; the bile acid chenodeoxycholate also increased in response to RE in muscle opposing previous findings in blood. Resistance training led to muscle hypertrophy, with slow type I and fast/intermediate type II muscle fibre diameter increasing by 10.7% and 10.4%, respectively. Comparison of post-exercise metabolite levels between trained and untrained state revealed alterations of 46 metabolites, including decreased N-acetylated ketogenic amino acids and increased beta-citrylglutamate which might support growth. Only five of the metabolites that changed after acute exercise in the untrained state were altered after chronic training, indicating that training induces multiple metabolic changes not directly related to the acute exercise response. Conclusion: The human skeletal muscle metabolome is sensitive towards acute RE in the trained and untrained states and reflects a broad range of adaptive processes in response to repeated stimulation.


2004 ◽  
Vol 287 (2) ◽  
pp. R322-R327 ◽  
Author(s):  
M. H. Stanley Chan ◽  
Andrew L. Carey ◽  
Matthew J. Watt ◽  
Mark A. Febbraio

To determine the expression and induction of cytokines in human skeletal muscle during concentric contractions, eight males performed 60 min of bicycle exercise, with either a normal (Con) or reduced (Lo Gly) preexercise intramuscular glycogen content. Muscle biopsy samples were obtained before and after exercise and analyzed for glycogen and the mRNA expression of 13 cytokines. Resting muscle glycogen was higher ( P < 0.05) in Con compared with Lo Gly and was reduced ( P < 0.05) to 102 ± 32 vs. 17 ± 5 mmol U glycosyl/kg dry mass for Con and Lo Gly, respectively. We detected mRNA levels in human skeletal muscle for five cytokines, namely interleukin (IL)-1β, IL-6, IL-8, IL-15, and tumor necrosis factor-α. However, muscle contraction increased ( P < 0.05) the mRNA expression of IL-6 and IL-8 alone. In addition, the fold change for both IL-8 and IL-6 was markedly higher ( P < 0.05) in Lo Gly compared with Con. Given these results, we analyzed venous blood samples, obtained before and during exercise, for IL-6 and IL-8. Plasma IL-6 was not different at rest, and although the circulating concentration of this cytokine increased ( P < 0.05) it increased to a greater extent ( P < 0.05) throughout exercise in Lo Gly. In contrast, plasma IL-8 was not affected by exercise or treatment. These data demonstrate that cytokines are not ubiquitously expressed in skeletal muscle and that only IL-6 and IL-8 mRNA are increased during contraction of this mode and duration. Furthermore, the mRNA abundance of IL-6 and IL-8 appears to be influenced by glycogen availability in the contracting muscle.


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