The peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) is abundantly expressed in trained muscles and regulates muscle adaptation to endurance exercise. Inversely, mice lacking a functional PGC-1 alpha allele in muscle exhibit reduced muscle functionality and increased inflammation. In isolated muscle cells, PGC-1 alpha and the related FCC-1 beta counteract the induction of inflammation by reducing the activity of the nuclear factor kappa B (NE kappa B). We now tested the effects of these metabolic regulators on inflammatory reactions in muscle tissue of control and muscle-specific PGC-1 alpha/-1 beta 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-1 s 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. (C) 2015 Elsevier Inc. All rights reserved.