The peroxisome proliferator-activated receptor ? coactivator 1?/? (PGC-1) coactivators repress the transcriptional activity of NF-?B in skeletal muscle cells.

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 ? coactivator (PGC) 1?, whereas its loss correlates with propagation of local and systemic inflammatory markers. We examined the influence of PGC-1? and the related PGC-1? on inflammatory cytokines upon stimulation of muscle cells with TNF?, Toll-like receptor agonists, and free fatty acids. PGC-1s differentially repressed expression of proinflammatory cytokines by targeting NF-?B signaling. Interestingly, PGC-1? and PGC-1? both reduced phoshorylation of the NF-?B 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.

SUBMITTER: Eisele PS 

PROVIDER: S-EPMC3554897 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature