title: The PGC-1 coactivators promote an anti-inflammatory environment in skeletal muscle in vivo.
abstract: The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is abundantly expressed in trained muscles and regulates muscle adaptation to endurance exercise. Inversely, mice lacking a functional PGC-1α allele in muscle exhibit reduced muscle functionality and increased inflammation. In isolated muscle cells, PGC-1α and the related PGC-1β counteract the induction of inflammation by reducing the activity of the nuclear factor κB (NFκB). We now tested the effects of these metabolic regulators on inflammatory reactions in muscle tissue of control and muscle-specific PGC-1α/-1β transgenic mice in vivo in the basal state as well as after an acute inflammatory insult. Surprisingly, we observed a PGC-1-dependent alteration of the cytokine profile characterized by an increase in anti-inflammatory factors and a strong suppression of the pro-inflammatory interleukin 12 (IL-12). In conclusion, the anti-inflammatory environment in muscle that is promoted by the PGC-1s might contribute to the beneficial effects of these coactivators on muscle function and provides a molecular link underlying the tight mutual regulation of metabolism and inflammation.
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Petra Sabine
authors.initials: PS
authors.lastname: Eisele
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Regula
authors.initials: R
authors.lastname: Furrer
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Beer
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich, Switzerland. Electronic address: christoph.handschin@unibas.ch.
authors.forename: Christoph
authors.initials: C
authors.lastname: Handschin
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12
keywords: Inflammation; Metabolism; Mitochondria; PGC-1; Skeletal muscle