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The peroxisome proliferator-activated receptor γ coactivator 1α/β (PGC-1) coactivators repress the transcriptional activity of NF-κB in skeletal muscle cells


Eisele, Petra S; Salatino, Silvia; Sobek, Jens; Hottiger, Michael O; Handschin, Christoph (2013). The peroxisome proliferator-activated receptor γ coactivator 1α/β (PGC-1) coactivators repress the transcriptional activity of NF-κB in skeletal muscle cells. Journal of Biological Chemistry, 288(4):2246-2260.

Abstract

A persistent, low-grade inflammation accompanies many chronic diseases that are promoted by physical inactivity and improved by exercise. The beneficial effects of exercise are mediated in large part by peroxisome proliferator-activated receptor γ coactivator (PGC) 1α, whereas its loss correlates with propagation of local and systemic inflammatory markers. We examined the influence of PGC-1α and the related PGC-1β on inflammatory cytokines upon stimulation of muscle cells with TNFα, Toll-like receptor agonists, and free fatty acids. PGC-1s differentially repressed expression of proinflammatory cytokines by targeting NF-κB signaling. Interestingly, PGC-1α and PGC-1β both reduced phoshorylation of the NF-κB family member p65 and thereby its transcriptional activation potential. Taken together, the data presented here show that the PGC-1 coactivators are able to constrain inflammatory events in muscle cells and provide a molecular link between metabolic and immune pathways. The PGC-1s therefore represent attractive targets to not only improve metabolic health in diseases like type 2 diabetes but also to limit the detrimental, low-grade inflammation in these patients.

Abstract

A persistent, low-grade inflammation accompanies many chronic diseases that are promoted by physical inactivity and improved by exercise. The beneficial effects of exercise are mediated in large part by peroxisome proliferator-activated receptor γ coactivator (PGC) 1α, whereas its loss correlates with propagation of local and systemic inflammatory markers. We examined the influence of PGC-1α and the related PGC-1β on inflammatory cytokines upon stimulation of muscle cells with TNFα, Toll-like receptor agonists, and free fatty acids. PGC-1s differentially repressed expression of proinflammatory cytokines by targeting NF-κB signaling. Interestingly, PGC-1α and PGC-1β both reduced phoshorylation of the NF-κB family member p65 and thereby its transcriptional activation potential. Taken together, the data presented here show that the PGC-1 coactivators are able to constrain inflammatory events in muscle cells and provide a molecular link between metabolic and immune pathways. The PGC-1s therefore represent attractive targets to not only improve metabolic health in diseases like type 2 diabetes but also to limit the detrimental, low-grade inflammation in these patients.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
05 Vetsuisse Faculty > Department of Molecular Mechanisms of Disease
07 Faculty of Science > Department of Molecular Mechanisms of Disease
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:2013
Deposited On:28 Jan 2014 14:06
Last Modified:22 Nov 2017 16:10
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in Eisele, Petra S; Salatino, Silvia; Sobek, Jens; Hottiger, Michael O; Handschin, Christoph (2013). The peroxisome proliferator-activated receptor γ coactivator 1α/β (PGC-1) coactivators repress the transcriptional activity of NF-κB in skeletal muscle cells. Journal of Biological Chemistry, 288:2246-2260. © the American Society for Biochemistry and Molecular Biology.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1074/jbc.M112.375253
PubMed ID:23223635

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