PPAR <gamma> as a molecular target of EPA anti-inflammatory activity during TNF-<alpha>-impaired skeletal muscle cell differentiation

Magee, P; Pearson, S; Whittingham-Dowd, J; Allen, JT

Abstract

Activated skeletal muscle satellite cells facilitate muscle repair or growth through proliferation, differentiation and fusion into new or existing myotubes. Elevated levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) impair this process and are documented to have significant roles in muscle pathology. Recent evidence shows that the ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) can block TNF-mediated suppression of progenitor cell differentiation, but the nature of this activity and its significance for local regulation of inflammation are not known. In the current study, we examined differentiation of the C2C12 myoblast line during treatment with TNF-α and EPA and measured the expression, activation and inhibition of peroxisome proliferator-activated receptor-γ (PPARγ), as several studies have shown its involvement in mediating EPA activity and the inhibition of nuclear factor (NF)-κB inflammatory gene activation. We found that TNF-α treatment increased NF-κB activity and reduced expression and activation of PPARγ, resulting in impaired myotube formation. EPA treatment attenuated these effects of TNF-α and was associated with up-regulation of PPARγ. Furthermore, EPA inhibited TNF-α-mediated transcription and secretion of interleukin (IL)-6, a key target gene of TNF-mediated NF-κB transcriptional activity. Pretreatment with a PPARγ selective antagonist inhibited some of the actions of EPA but was only partially effective in reversing inhibition of IL-6 production. These results show that EPA activity was associated with altered expression and activation of PPARγ, but exerted through both PPARγ-dependent and PPARγ-independent pathways leading to suppression of the proinflammatory cellular microenvironment.

Citation

Magee, P., Pearson, S., Whittingham-Dowd, J., & Allen, J. (2012). PPAR as a molecular target of EPA anti-inflammatory activity during TNF--impaired skeletal muscle cell differentiation. Journal of Nutritional Biochemistry, 23(11), 1440-1448. https://doi.org/10.1016/j.jnutbio.2011.09.005

• Journal Article Type: Article
• Acceptance Date: Sep 16, 2011
• Online Publication Date: Feb 1, 2012
• Publication Date: Nov 1, 2012
• Deposit Date: Oct 6, 2011
• Journal: The Journal of Nutritional Biochemistry
• Print ISSN: 0955-2863
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 11
• Pages: 1440-1448
• DOI: https://doi.org/10.1016/j.jnutbio.2011.09.005
• Publisher URL: https://doi.org/10.1016/j.jnutbio.2011.09.005
• Related Public URLs: https://www.sciencedirect.com/journal/the-journal-of-nutritional-biochemistry