PPARγ as a molecular target of EPA anti-inflammatory activity during TNF-α-impaired skeletal muscle cell differentiation

Biomedical and Life Sciences

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https://doi.org/10.1016/j.jnutbio.2011.09.005
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Keywords

Animals, Anti-Inflammatory Agents, Non-Steroidal, Cell Differentiation, Cell Line, Eicosapentaenoic Acid, Gene Expression Regulation, Interleukin-6, Mice, Muscle, Skeletal, NF-kappa B, PPAR gamma, Tumor Necrosis Factor-alpha, Journal Article, Research Support, Non-U.S. Gov't

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PPARγ as a molecular target of EPA anti-inflammatory activity during TNF-α-impaired skeletal muscle cell differentiation. / Magee, Peter; Pearson, Stephen; Whittingham-Dowd, Jayde et al.
In: The Journal of nutritional biochemistry, Vol. 23, No. 11, 11.11.2012, p. 1440-1448.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Bibtex

@article{40dabe8cb2d841ecbc6fba15c21f8705,

title = "PPARγ as a molecular target of EPA anti-inflammatory activity during TNF-α-impaired skeletal muscle cell differentiation",

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.",

keywords = "Animals, Anti-Inflammatory Agents, Non-Steroidal, Cell Differentiation, Cell Line, Eicosapentaenoic Acid, Gene Expression Regulation, Interleukin-6, Mice, Muscle, Skeletal, NF-kappa B, PPAR gamma, Tumor Necrosis Factor-alpha, Journal Article, Research Support, Non-U.S. Gov't",

author = "Peter Magee and Stephen Pearson and Jayde Whittingham-Dowd and Jeremy Allen",

year = "2012",

month = nov,

day = "11",

doi = "10.1016/j.jnutbio.2011.09.005",

language = "English",

volume = "23",

pages = "1440--1448",

journal = "The Journal of nutritional biochemistry",

issn = "0955-2863",

publisher = "Elsevier Inc.",

number = "11",

}

RIS

TY - JOUR

T1 - PPARγ as a molecular target of EPA anti-inflammatory activity during TNF-α-impaired skeletal muscle cell differentiation

AU - Magee, Peter

AU - Pearson, Stephen

AU - Whittingham-Dowd, Jayde

AU - Allen, Jeremy

PY - 2012/11/11

Y1 - 2012/11/11

N2 - 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.

AB - 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.

KW - Animals

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Cell Differentiation

KW - Cell Line

KW - Eicosapentaenoic Acid

KW - Gene Expression Regulation

KW - Interleukin-6

KW - Mice

KW - Muscle, Skeletal

KW - NF-kappa B

KW - PPAR gamma

KW - Tumor Necrosis Factor-alpha

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jnutbio.2011.09.005

DO - 10.1016/j.jnutbio.2011.09.005

M3 - Journal article

C2 - 22305406

VL - 23

SP - 1440

EP - 1448

JO - The Journal of nutritional biochemistry

JF - The Journal of nutritional biochemistry

SN - 0955-2863

IS - 11

ER -

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