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closeConfirmative article with data in vivo
Posted by MyMuscle on 28 Feb 2012 at 15:27 GMT
This article shows that a pro-inflammatory role of PGC-1 in cultured muscle cells. A new article by Olesen et al here in PLoS ONE now proves these data directly in vivo in mice. The picture is getting clearer.
PGC-1, NF kappa B, myokines and inflammation
Franky replied to MyMuscle on 27 Jul 2012 at 13:09 GMT
It's unfortunately a bit more complicated than that.
There are strong data from mouse models with overexpression of PGC-1 showing that PGC-1 activates the NF kappa B signaling pathway. PGC-1 activates two upstream regulators of NF kappa B: Akt (Romanino et al PNAS 2012) and calcineurin (Summermatter et al Am J Physiol Cell Physiol 2012).
This results in increased NF kappa B phosphorylation (Olesen et al PLOS ONE 2012).
However, there are also some data reporting the opposite (Wenz et al PNAS 2009). Although this seems to be true mainly for very old mice and the NF kappa B pathway has not been studied in detail in the study.
Regarding other inflammatory processes it has to be considered that PGC-1 regulates many genes. In this article some are listed which exert proinflammatory actions.
On the other hand, PGC-1 is a coactivator of PPARs which are well known to act antiinflammatory (Wahli and Michalik Trends Endocrinol Metab 2012). PPARbeta/delta which exerts almost the same functions as PGC-1 reduces diacylglycerol levels and prevents the activation of NF kappa B (Wahli and Michalik Trends Endocrinol Metab 2012).
Overexpression of PGC-1 increases the levels of highly antinflammatory PPAR alpha which then increases TRB3.
Taken together PGC-1 does not has a pro- or antiinflammatory effect. There is a mixed pattern and PGC-1 leads to the transcription of some pro-, but also of some antiinflammatory genes.
NF kappa B and PPARs are certainly central for these effects.
For that reason, the whole thing is a bit more complex. Of one thing we have to be aware: Skeletal muscle is not a major contributor to inflammatory processes and so far although people have reported changes in some pro or antiinflammatory genes in muscle, nobody has ever shown any physiological relevance of such findings or any effect on overall inflammation