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 PGC-1 muscle metabolism and inflammation

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Steve
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PostSubject: PGC-1 muscle metabolism and inflammation   Sat Jun 04, 2011 5:08 am

The molecule PGC-1 seems to be a very important player in muscle.
I want to give here a quick overview on its physiological role.
PGC-1 does on the positive side:
- increase mitochondrial biogenesis
- increase oxidation
- protects against sarcopenia
- increases exercise performance
- increase energy storage (glycogen and lipid)

PGC-1 does on the negative side:
- increase inflammation

Several researchers show interaction of PGC-1 with p65 also named NF kappa B.
PGC-1 reduces p65, but nonethless PGC-1 in muscle is proinflammatory. There is increase in TNF.
PGC-1 induces more markers of inflammation.

We believe it is not a good physiological target for medical treatment

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Annicko
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PostSubject: PGC-1 {alpha} PGC-1 {beta} and inflammation   Wed Jul 13, 2011 10:58 pm

@ Steve
I share the same opinion. Researchers try desperately to convince us of the positive effects of these transcriptional activators, but they just ignore that not everything is good.
For example it has been shown that:
- PGC-1 members can also cause muscle atrophy when too high
- induce insulin resistance when too high
- promote lipid accumulation in non-adipose tissue
- cause inflammatory responses.

The link between PGC-1 {alpha} and {beta} and inflammation is pretty new, but very worrying. Olesen et al have shown that PGC-1 is highly proinflammatory at basal states and it is even much worse after induction of further inflammation by Lipopolysaccharide (LPS). There is increase in muscle tumor necrosis factor {alpha} (TNF {alpha} expression in muscle and increase in TNF release into to plasma!
other groups report similar problems. They show that although p65 (NF {kappa} B is lower when PGC-1 is high, but on the other hand TNF is much higher. When TNF or LPS are injected into the muscle the levels of TNF production and release even increase further (positive feedback).
Then also when PGC-1 levels are high, there is a high Interleukin (IL) production. Like IL-6. Markers of macrophage infiltration like cluster of differentiation (CDxx) are elevated.

Altogether PGC-1 has positive effects, but researchers should not hide all negative impacts.
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Kerstin



Number of posts : 1
Location : University
Occupation : Researcher
Educational Qualification : PhD
Registration date : 2011-08-16

PostSubject: Re: PGC-1 muscle metabolism and inflammation   Tue Aug 16, 2011 1:24 am

You are both absolutely right and you started a very interesting discussion. In the meantime there is even more information on the issue of PGC-1 and inflammation. This adds further proof to what Anniko already described:

PGC-1α and β are activators of mitochondrial biogenesis and master regulators of muskuloskeletal metabolism. Recently, they have been suggested to modulate inflammatory responses. Studies were undertaken to unravel the role of PGC-1 isoforms on inflammatory processes. Inflammation was induced by intramuscular injection of lipopolysaccharide (LPS) or tumour necrosis factor α (TNFα) into mice transgenic for PGC-1α or β. The results show that: 1) Overexpression of PGC-1 exerts distinct inflammatory effects. On the one hand PGC-1 reduces the basal levels of pro-inflammatory p65 (NFκB), while on the other hand it increases the basal levels of pro-inflammatory TNFα. 2) Injection of LPS or TNFα lead to strong inflammation, but the differential pattern already observed at the basal state remains. 3) LPS/TNF stimulate the infiltration of macrophages into muscle tissue more in transgenic than in wild-type mice. We conclude that PGC-1 does exert a mixed effect on inflammation. overexpression of PGC-1 stimulate, but also represses pro-inflammatory markers. The data suggest that no direct interaction between PGC-1 and
inflammatory processes occurs. Rather, inflammation seems to occur secondarily and artefactually to the transgene expression. Differences observed after stumilation by LPS/TNFα represent carry-over effects of the artefactual changes in the basal state.
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PostSubject: Re: PGC-1 muscle metabolism and inflammation   Today at 9:11 pm

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