Skeletal muscle PGC-1a is required for maintaining an acute LPS-induced TNFa response

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Skeletal muscle PGC-1a is required for maintaining an acute LPS-induced TNFa response. / Olesen, Jesper; Larsson, Signe; Iversen, Ninna; Yousafzai, Simi; Hellsten, Ylva; Pilegaard, Henriette.

In: P L o S One, Vol. 7, No. 2, 2012, p. e32222.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Olesen, J, Larsson, S, Iversen, N, Yousafzai, S, Hellsten, Y & Pilegaard, H 2012, 'Skeletal muscle PGC-1a is required for maintaining an acute LPS-induced TNFa response', P L o S One, vol. 7, no. 2, pp. e32222. https://doi.org/10.1371/journal.pone.0032222

APA

Olesen, J., Larsson, S., Iversen, N., Yousafzai, S., Hellsten, Y., & Pilegaard, H. (2012). Skeletal muscle PGC-1a is required for maintaining an acute LPS-induced TNFa response. P L o S One, 7(2), e32222. https://doi.org/10.1371/journal.pone.0032222

Vancouver

Olesen J, Larsson S, Iversen N, Yousafzai S, Hellsten Y, Pilegaard H. Skeletal muscle PGC-1a is required for maintaining an acute LPS-induced TNFa response. P L o S One. 2012;7(2):e32222. https://doi.org/10.1371/journal.pone.0032222

Author

Olesen, Jesper ; Larsson, Signe ; Iversen, Ninna ; Yousafzai, Simi ; Hellsten, Ylva ; Pilegaard, Henriette. / Skeletal muscle PGC-1a is required for maintaining an acute LPS-induced TNFa response. In: P L o S One. 2012 ; Vol. 7, No. 2. pp. e32222.

Bibtex

@article{6d81108efa65443aa4392c0faf6dac97,
title = "Skeletal muscle PGC-1a is required for maintaining an acute LPS-induced TNFa response",
abstract = "Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor ¿ coactivator (PGC)-1a has been suggested to be protective against low-grade inflammation. However, whether these anti-inflammatory properties affect acute inflammation is not known. The aim of the present study was therefore to investigate the role of muscle PGC-1a in acute inflammation. Quadriceps muscles were removed from 10-week old whole body PGC-1a knockout (KO), muscle specific PGC-1a KO (MKO) and muscle-specific PGC-1a overexpression mice (TG), 2 hours after an intraperitoneal injection of either 0.8 µg LPS/g body weight or saline. Basal TNFa mRNA content was lower in skeletal muscle of whole body PGC-1a KO mice and in accordance TG mice showed increased TNFa mRNA and protein level relative to WT, indicating a possible PGC-1a mediated regulation of TNFa. Basal p65 phosphorylation was increased in TG mice possibly explaining the elevated TNFa expression in these mice. Systemically, TG mice had reduced basal plasma TNFa levels compared with WT suggesting a protective effect against systemic low-grade inflammation in these animals. While TG mice reached similar TNFa levels as WT and showed more marked induction in plasma TNFa than WT after LPS injection, MKO PGC-1a mice had a reduced plasma TNFa and skeletal muscle TNFa mRNA response to LPS. In conclusion, the present findings suggest that PGC-1a enhances basal TNFa expression in skeletal muscle and indicate that PGC-1a does not exert anti-inflammatory effects during acute inflammation. Lack of skeletal muscle PGC-1a seems however to impair the acute TNFa response, which may reflect a phenotype more susceptible to infections as also observed in type 2 diabetes patients.",
author = "Jesper Olesen and Signe Larsson and Ninna Iversen and Simi Yousafzai and Ylva Hellsten and Henriette Pilegaard",
note = "CURIS 2012 5200 033",
year = "2012",
doi = "10.1371/journal.pone.0032222",
language = "English",
volume = "7",
pages = "e32222",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

RIS

TY - JOUR

T1 - Skeletal muscle PGC-1a is required for maintaining an acute LPS-induced TNFa response

AU - Olesen, Jesper

AU - Larsson, Signe

AU - Iversen, Ninna

AU - Yousafzai, Simi

AU - Hellsten, Ylva

AU - Pilegaard, Henriette

N1 - CURIS 2012 5200 033

PY - 2012

Y1 - 2012

N2 - Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor ¿ coactivator (PGC)-1a has been suggested to be protective against low-grade inflammation. However, whether these anti-inflammatory properties affect acute inflammation is not known. The aim of the present study was therefore to investigate the role of muscle PGC-1a in acute inflammation. Quadriceps muscles were removed from 10-week old whole body PGC-1a knockout (KO), muscle specific PGC-1a KO (MKO) and muscle-specific PGC-1a overexpression mice (TG), 2 hours after an intraperitoneal injection of either 0.8 µg LPS/g body weight or saline. Basal TNFa mRNA content was lower in skeletal muscle of whole body PGC-1a KO mice and in accordance TG mice showed increased TNFa mRNA and protein level relative to WT, indicating a possible PGC-1a mediated regulation of TNFa. Basal p65 phosphorylation was increased in TG mice possibly explaining the elevated TNFa expression in these mice. Systemically, TG mice had reduced basal plasma TNFa levels compared with WT suggesting a protective effect against systemic low-grade inflammation in these animals. While TG mice reached similar TNFa levels as WT and showed more marked induction in plasma TNFa than WT after LPS injection, MKO PGC-1a mice had a reduced plasma TNFa and skeletal muscle TNFa mRNA response to LPS. In conclusion, the present findings suggest that PGC-1a enhances basal TNFa expression in skeletal muscle and indicate that PGC-1a does not exert anti-inflammatory effects during acute inflammation. Lack of skeletal muscle PGC-1a seems however to impair the acute TNFa response, which may reflect a phenotype more susceptible to infections as also observed in type 2 diabetes patients.

AB - Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor ¿ coactivator (PGC)-1a has been suggested to be protective against low-grade inflammation. However, whether these anti-inflammatory properties affect acute inflammation is not known. The aim of the present study was therefore to investigate the role of muscle PGC-1a in acute inflammation. Quadriceps muscles were removed from 10-week old whole body PGC-1a knockout (KO), muscle specific PGC-1a KO (MKO) and muscle-specific PGC-1a overexpression mice (TG), 2 hours after an intraperitoneal injection of either 0.8 µg LPS/g body weight or saline. Basal TNFa mRNA content was lower in skeletal muscle of whole body PGC-1a KO mice and in accordance TG mice showed increased TNFa mRNA and protein level relative to WT, indicating a possible PGC-1a mediated regulation of TNFa. Basal p65 phosphorylation was increased in TG mice possibly explaining the elevated TNFa expression in these mice. Systemically, TG mice had reduced basal plasma TNFa levels compared with WT suggesting a protective effect against systemic low-grade inflammation in these animals. While TG mice reached similar TNFa levels as WT and showed more marked induction in plasma TNFa than WT after LPS injection, MKO PGC-1a mice had a reduced plasma TNFa and skeletal muscle TNFa mRNA response to LPS. In conclusion, the present findings suggest that PGC-1a enhances basal TNFa expression in skeletal muscle and indicate that PGC-1a does not exert anti-inflammatory effects during acute inflammation. Lack of skeletal muscle PGC-1a seems however to impair the acute TNFa response, which may reflect a phenotype more susceptible to infections as also observed in type 2 diabetes patients.

U2 - 10.1371/journal.pone.0032222

DO - 10.1371/journal.pone.0032222

M3 - Journal article

C2 - 22384185

VL - 7

SP - e32222

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 2

ER -

ID: 38264398