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. 2024 Jan 29:694:149413.
doi: 10.1016/j.bbrc.2023.149413. Epub 2023 Dec 20.

Role of PPARα in inflammatory response of C2C12 myotubes

Yuki Shimizu  1 , Keiko Hamada  1 , Tingting Guo  1 , Chie Hasegawa  1 , Yusuke Kuga  1 , Katsushi Takeda  1 , Takashi Yagi  1 , Hiroyuki Koyama  1 , Hiroshi Takagi  2 , Daisuke Aotani  1 , Hiromi Kataoka  1 , Tomohiro Tanaka  3
Affiliations

Role of PPARα in inflammatory response of C2C12 myotubes

Yuki Shimizu et al. Biochem Biophys Res Commun. .

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.

Keywords: Inflammation; PGC-1α; PPAR; Pemafibrate; Sarcopenia; Skeletal muscle.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tomohiro Tanaka reports a relationship with Kowa Company Ltd that includes: speaking and lecture fees. All the other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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