Role of PPAR in inflammatory response of C2C12 myotubes

Recent studies have shown a role of inflammation in muscle atrophy and sarcopenia. However, no antiinflammatory pharmacotherapy has been established for the treatment of sarcopenia. Here, we investigate the potential role of PPAR alpha and its ligands on inflammatory response and PGC-1 alpha gene expression in LPS-treated C2C12 myotubes. Knockdown of PPAR alpha, whose expression was upregulated upon differentiation, augmented IL-6 or TNF alpha gene expression. Conversely, PPAR alpha overexpression or its activation by ligands suppressed 2-h LPSinduced cytokine expression, with pemafibrate attenuating NF-kappa B or STAT3 phosphorylation. Of note, reduction of PGC-1 alpha gene expression by LPS treatment for 24 hours was partially reversed by fenofibrate. Our data demonstrate a critical inhibitory role of PPAR alpha in inflammatory response of C2C12 myotubes and suggest a future possibility of PPAR alpha ligands as a candidate for anti-inflammatory therapy against sarcopenia.