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Role of PPARα in inflammatory response of C2C12 myotubes
Yuki Shimizu1, Keiko Hamada1, Tingting Guo1
1Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 457-8601, Japan.
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.
Insights
Peroxisome proliferator-activated receptor alpha (PPARα) inhibits inflammation in muscle cells. PPARα ligands show potential as anti-inflammatory therapies for sarcopenia, a condition linked to muscle inflammation.
Area of Science:
- Muscle physiology and cellular biology
- Inflammation and immunology
- Pharmacology and drug discovery
Background:
- Inflammation is implicated in muscle atrophy and sarcopenia.
- Current anti-inflammatory treatments for sarcopenia are lacking.
- Peroxisome proliferator-activated receptor alpha (PPARα) role in muscle inflammation is under investigation.
Purpose of the Study:
- To investigate the role of PPARα and its ligands in modulating inflammatory responses in muscle cells.
- To examine the effect of PPARα on PGC-1α gene expression under inflammatory conditions.
- To explore the therapeutic potential of PPARα ligands for sarcopenia treatment.
Main Methods:
- Utilized LPS-treated C2C12 myotubes to model inflammation.
- Employed PPARα knockdown and overexpression techniques.
- Administered PPARα ligands (pemafibrate, fenofibrate) and assessed inflammatory markers (IL-6, TNFα) and signaling pathways (NF-κB, STAT3 phosphorylation).
Main Results:
- PPARα knockdown exacerbated IL-6 and TNFα gene expression.
- PPARα activation by ligands suppressed LPS-induced cytokine expression.
- Fenofibrate partially reversed LPS-induced reduction in PGC-1α gene expression.
Conclusions:
- PPARα plays a critical inhibitory role in the inflammatory response of C2C12 myotubes.
- PPARα ligands demonstrate potential as anti-inflammatory agents.
- PPARα ligands may offer a novel therapeutic strategy for sarcopenia.
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