1. Role of PPARα in inflammatory response of C2C12 myotubes.
- Author
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Shimizu, Yuki, Hamada, Keiko, Guo, Tingting, Hasegawa, Chie, Kuga, Yusuke, Takeda, Katsushi, Yagi, Takashi, Koyama, Hiroyuki, Takagi, Hiroshi, Aotani, Daisuke, Kataoka, Hiromi, and Tanaka, Tomohiro
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INFLAMMATION , *MYOSITIS , *MUSCULAR atrophy , *GENE expression , *SARCOPENIA - Abstract
Recent studies have shown a role of inflammation in muscle atrophy and sarcopenia. However, no anti-inflammatory pharmacotherapy has been established for the treatment of sarcopenia. Here, we investigate the potential role of PPARα and its ligands on inflammatory response and PGC-1α gene expression in LPS-treated C2C12 myotubes. Knockdown of PPARα, whose expression was upregulated upon differentiation, augmented IL-6 or TNFα gene expression. Conversely, PPARα overexpression or its activation by ligands suppressed 2-h LPS-induced cytokine expression, with pemafibrate attenuating NF-κB or STAT3 phosphorylation. Of note, reduction of PGC-1α gene expression by LPS treatment for 24 hours was partially reversed by fenofibrate. Our data demonstrate a critical inhibitory role of PPARα in inflammatory response of C2C12 myotubes and suggest a future possibility of PPARα ligands as a candidate for anti-inflammatory therapy against sarcopenia. [Display omitted] • Endogenous PPARα is a suppressor of inflammation in C2C12 myotubes. • PPARα activation by fenofibrate or pemafibrate suppresses inflammation by LPS. • Dose dependency for fenofibrate or pemafibrate observed for IL-6 suppression. • PGC-1α expression in myotubes is suppressed by 24-h long-term LPS treatment. • PGC-1α suppression by long-term LPS is rescued by fenofibrate but not by pemafibrate. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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