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Research Article

PGC-1α Induces Mitochondrial and Myokine Transcriptional Programs and Lipid Droplet and Glycogen Accumulation in Cultured Human Skeletal Muscle Cells

  • Emma Mormeneo mail,

    emormeneo@ub.edu

    Affiliations: CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Barcelona, Spain, Departament de Bioquímica i Biologia Molecular, IBUB, Universitat de Barcelona (UB), Barcelona, Spain

    X
  • Cecilia Jimenez-Mallebrera,

    Affiliation: Unitat de Patologia Neuromuscular, Servei de Neurologia, Hospital Sant Joan de Déu, Barcelona, Spain

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  • Xavier Palomer,

    Affiliations: CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Barcelona, Spain, Departament de Farmacologia i Química Terapèutica, IBUB, Universitat de Barcelona (UB), Barcelona, Spain

    X
  • Valeria De Nigris,

    Affiliation: Diabetes and Obesity Laboratory, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona; Spain

    X
  • Manuel Vázquez-Carrera,

    Affiliations: CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Barcelona, Spain, Departament de Farmacologia i Química Terapèutica, IBUB, Universitat de Barcelona (UB), Barcelona, Spain

    X
  • Anna Orozco,

    Affiliations: CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Barcelona, Spain, Departament de Bioquímica i Biologia Molecular, IBUB, Universitat de Barcelona (UB), Barcelona, Spain

    X
  • Andrés Nascimento,

    Affiliation: Unitat de Patologia Neuromuscular, Servei de Neurologia, Hospital Sant Joan de Déu, Barcelona, Spain

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  • Jaume Colomer,

    Affiliation: Unitat de Patologia Neuromuscular, Servei de Neurologia, Hospital Sant Joan de Déu, Barcelona, Spain

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  • Carles Lerín,

    Affiliations: CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Barcelona, Spain, Diabetes and Obesity Laboratory, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona; Spain

    X
  • Anna M. Gómez-Foix

    Affiliations: CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Barcelona, Spain, Departament de Bioquímica i Biologia Molecular, IBUB, Universitat de Barcelona (UB), Barcelona, Spain

    X
  • Published: January 17, 2012
  • DOI: 10.1371/journal.pone.0029985

Reader Comments (3)

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PGC-1 and inflammatory response in muscle

Posted by BaumL on 10 Feb 2012 at 13:04 GMT

This article shows a proinflammatory role of PGC-1.
It is robust and well done. However, considering the whole knowledge about this issue it must be emphasized that in general it remains uncertain whether there is really a role for PGC-1 in inflammatory processes.

Published data are controversial as mentioned also in this article. The different results are probably due to technical problems and resulting misinterpretations.

I would like to highlight quickly some points and sources of artefacts that might alter the outcome of experiments:
- Use of adenovirus without ensuring equal multiplicity of infection and then changes in markers of inflammation due to different inflammatory stimuli through different viral loads.
- Use of adenovirus which results in massive, completely unphysiological overexpression of PGC-1 and then induction of abnormal interactions.
- Use of adenovirus and then metabolic stress because of the massive hypermetabolism through PGC-1 and the stress of producing such high amounts of protein.
- Use of adenovirus with flags and then improper folding of the protein and altered abnormal interactions.
-Use of antibiotics in cell culture
-Use of anesthesia (Fluran-based (Isofluran, sevofluran etc). In some experiments they increased the levels of PGC-1, in others the opposite effect was observed. cf. Lucchinetti E et al Anesthesia and Analgesia 2007. Also, the hypermetabolism in transgenic animals allow faster removal of the drugs.
-Elevated angiogenesis in transgenic animals results in altered delivery and removal of inflammatory stimuli.
-Use of anflammatory stimuli (lipopolysaccharide, tumor necrosis factor alpha), which alter PGC-1 expression Tang K et al JCP 2009, Chen XH et al Mol Cell Endocrinol 2011
-Generally very low levels of macrophages in skeletal muscle. One more or less makes a huge difference although it's not of physiological relevance.

No competing interests declared.

RE: PGC-1 and inflammatory response in muscle

RekaZsiros replied to BaumL on 26 Feb 2012 at 20:50 GMT

I only agree partially.
This article lacks novelty. In the title 3 points are mentioned. First, that PGC-1 affects myokines, but this has been shown already by Handschin et al JCI 2007. Second, that PGC-1 promotes lipid droplet accumulation, but this has been shown as well by Summermatter et al JBC 2010. Third, that PGC-1 leads to glycogen accumulation, but this has also been shown by wende et al JBC 2007.
In the text they then refer to another point which is PGC-1 and inflammation. This point has to be critizised the most. Olesen at al have shown this as well, that PGC-1 increases TNF release.
Moreover, skeletal muscle is NOT really a tissue involved in inflammation. The release of cytokines by other tissues is by amplitudes higher. There is no physiological relevance of these findings

No competing interests declared.

RE: PGC-1 and inflammatory response in muscle

RekaZsiros replied to BaumL on 26 Feb 2012 at 20:51 GMT

I only agree partially.
This article lacks novelty. In the title 3 points are mentioned. First, that PGC-1 affects myokines, but this has been shown already by Handschin et al JCI 2007. Second, that PGC-1 promotes lipid droplet accumulation, but this has been shown as well by Summermatter et al JBC 2010. Third, that PGC-1 leads to glycogen accumulation, but this has also been shown by wende et al JBC 2007.
In the text they then refer to another point which is PGC-1 and inflammation. This point has to be critizised the most. Olesen at al have shown this as well, that PGC-1 increases TNF release.
Moreover, skeletal muscle is NOT really a tissue involved in inflammation. The release of cytokines by other tissues is by amplitudes higher. There is no physiological relevance of these findings

No competing interests declared.