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.

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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