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The single nucleotide polymorphism Gly482Ser in the PGC-1α gene impairs exercise-induced slow-twitch muscle fibre transformation in humans.

Steinbacher P, Feichtinger RG, Kedenko L, Kedenko I, Reinhardt S, Schönauer AL, Leitner I, Sänger AM, Stoiber W, Kofler B, Förster H, Paulweber B, Ring-Dimitriou S - PLoS ONE (2015)

Bottom Line: Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes.Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups.These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Paris Lodron-University of Salzburg, Salzburg, Austria.

ABSTRACT
PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.

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Relative changes [%] of muscle characteristics in response to the 10 weeks endurance training programme.(A) Control individuals (GT1) show a significant increase of the slow fibre proportion after training while carriers of SNP Gly482Ser (GT2) are unaffected. (B) There is no difference between GT1 and GT2 in the increase of capillaries. (C) Controls (GT1) and SNP carriers (GT2) exhibit no significant differences in the training-induced increases in volume density of slow fibre mitochondria and intramyocellular lipid (IMCL). (D) The increases of fast fibre mitochondria and IMCL are also similar in GT1 and GT2. (E) Similarly, post-training increases in amounts of mitochondria as indicated by the activities of CS and OXPHOS enzymes do not significantly diverge between GT1 and GT2. GT1 (n = 13), GT2 (n = 15); data given as means ± SE; * intergroup differences significant at p < 0.05.
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pone.0123881.g002: Relative changes [%] of muscle characteristics in response to the 10 weeks endurance training programme.(A) Control individuals (GT1) show a significant increase of the slow fibre proportion after training while carriers of SNP Gly482Ser (GT2) are unaffected. (B) There is no difference between GT1 and GT2 in the increase of capillaries. (C) Controls (GT1) and SNP carriers (GT2) exhibit no significant differences in the training-induced increases in volume density of slow fibre mitochondria and intramyocellular lipid (IMCL). (D) The increases of fast fibre mitochondria and IMCL are also similar in GT1 and GT2. (E) Similarly, post-training increases in amounts of mitochondria as indicated by the activities of CS and OXPHOS enzymes do not significantly diverge between GT1 and GT2. GT1 (n = 13), GT2 (n = 15); data given as means ± SE; * intergroup differences significant at p < 0.05.

Mentions: Immunolabelling for fibre type-specific MHC isoforms served to analyse the relative proportion of slow (type I), fast (type II) and slow-fast hybrid muscle fibres within the biopsies (Fig 1A and 1B). On average, 773 muscle fibres per sample were analysed (range 308–1944). At baseline, the mean proportion of slow fibres in GT1 was 50.5 ± 2.5% and in GT2 59.9 ± 2.8% (p = 0.02, ANOVA, Table 2). After the training programme, the mean percentage of slow fibres in GT1 increased by 8.9 ± 2.6% which corresponds to a significant increase of 19% of the initial values (p < 0.01, Table 2, Fig 2A). By contrast, the relative numbers of slow fibres in GT2 decreased by 1.5 ± 2.6% (ns, Table 2, Fig 2A). Thus, only the control subjects that carry the major allele were capable of increasing the slow fibre frequency due to the training stimulus (p = 0.01, ANOVA, Table 2). The proportion of slow-fast hybrid fibres was very low (about 1.5% in both groups, Table 1) and showed no significant change after training (Table 2).


The single nucleotide polymorphism Gly482Ser in the PGC-1α gene impairs exercise-induced slow-twitch muscle fibre transformation in humans.

Steinbacher P, Feichtinger RG, Kedenko L, Kedenko I, Reinhardt S, Schönauer AL, Leitner I, Sänger AM, Stoiber W, Kofler B, Förster H, Paulweber B, Ring-Dimitriou S - PLoS ONE (2015)

Relative changes [%] of muscle characteristics in response to the 10 weeks endurance training programme.(A) Control individuals (GT1) show a significant increase of the slow fibre proportion after training while carriers of SNP Gly482Ser (GT2) are unaffected. (B) There is no difference between GT1 and GT2 in the increase of capillaries. (C) Controls (GT1) and SNP carriers (GT2) exhibit no significant differences in the training-induced increases in volume density of slow fibre mitochondria and intramyocellular lipid (IMCL). (D) The increases of fast fibre mitochondria and IMCL are also similar in GT1 and GT2. (E) Similarly, post-training increases in amounts of mitochondria as indicated by the activities of CS and OXPHOS enzymes do not significantly diverge between GT1 and GT2. GT1 (n = 13), GT2 (n = 15); data given as means ± SE; * intergroup differences significant at p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4401702&req=5

pone.0123881.g002: Relative changes [%] of muscle characteristics in response to the 10 weeks endurance training programme.(A) Control individuals (GT1) show a significant increase of the slow fibre proportion after training while carriers of SNP Gly482Ser (GT2) are unaffected. (B) There is no difference between GT1 and GT2 in the increase of capillaries. (C) Controls (GT1) and SNP carriers (GT2) exhibit no significant differences in the training-induced increases in volume density of slow fibre mitochondria and intramyocellular lipid (IMCL). (D) The increases of fast fibre mitochondria and IMCL are also similar in GT1 and GT2. (E) Similarly, post-training increases in amounts of mitochondria as indicated by the activities of CS and OXPHOS enzymes do not significantly diverge between GT1 and GT2. GT1 (n = 13), GT2 (n = 15); data given as means ± SE; * intergroup differences significant at p < 0.05.
Mentions: Immunolabelling for fibre type-specific MHC isoforms served to analyse the relative proportion of slow (type I), fast (type II) and slow-fast hybrid muscle fibres within the biopsies (Fig 1A and 1B). On average, 773 muscle fibres per sample were analysed (range 308–1944). At baseline, the mean proportion of slow fibres in GT1 was 50.5 ± 2.5% and in GT2 59.9 ± 2.8% (p = 0.02, ANOVA, Table 2). After the training programme, the mean percentage of slow fibres in GT1 increased by 8.9 ± 2.6% which corresponds to a significant increase of 19% of the initial values (p < 0.01, Table 2, Fig 2A). By contrast, the relative numbers of slow fibres in GT2 decreased by 1.5 ± 2.6% (ns, Table 2, Fig 2A). Thus, only the control subjects that carry the major allele were capable of increasing the slow fibre frequency due to the training stimulus (p = 0.01, ANOVA, Table 2). The proportion of slow-fast hybrid fibres was very low (about 1.5% in both groups, Table 1) and showed no significant change after training (Table 2).

Bottom Line: Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes.Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups.These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Paris Lodron-University of Salzburg, Salzburg, Austria.

ABSTRACT
PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.

Show MeSH
Related in: MedlinePlus