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Cited by 53Muscle Physiology and DisordersFatty Acid Research and HealthMeat and Animal Product Quality

Omega-3 fatty acid epa improves regenerative capacity of mouse skeletal muscle cells exposed to saturated fat and inflammation

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Saini, Amarjit, Sharples, Adam P., Al-Shanti, Nasser, Stewart, Claire E.·2017·Biogerontology
DOI 10.1007/s10522-016-9667-3PMC PMC5288450
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Abstract

Sarcopenic obesity is characterised by high fat mass, low muscle mass and an elevated inflammatory environmental milieu. We therefore investigated the effects of elevated inflammatory cytokine TNF-α (aging/obesity) and saturated fatty acid, palmitate (obesity) on skeletal muscle cells in the presence/absence of EPA, a-3 polyunsaturated fatty acid with proposed anti-inflammatory, anti-obesity activities. In the present study we show that palmitate was lipotoxic, inducing high levels of cell death and blocking myotube formation. Cell death under these conditions was associated with increased caspase activity, suppression of differentiation, reductions in both creatine kinase activity and gene expression of myogenic factors; IGF-II, IGFBP-5, MyoD and myogenin. However, inhibition of caspase activity via administration of Z-VDVAD-FMK (caspase-2), Z-DEVD-FMK (caspase-3) and ZIETD-KMK (caspase 8) was without effect on cell death. By contrast, lipotoxicity associated with elevated palmitate was reduced with the MEK inhibitor PD98059, indicating palmitate induced cell death was MAPK mediated. These lipotoxic conditions were further exacerbated in the presence of inflammation via TNF-α co-administration. Addition of EPA under cytotoxic stress (TNF-α) was shown to partially rescue differentiation with enhanced myotube formation being associated with increased MyoD, myogenin, IGF-II and IGFBP-5 expression. EPA had little impact on the cell death phenotype observed in lipotoxic conditions but did show benefit in restoring differentiation under lipotoxic plus cytotoxic conditions. Under these conditions Id3 (inhibitor of differentiation) gene expression was inversely linked with survival rates, potentially indicating a novel role of EPA and Id3 in the regulation of apoptosis in lipotoxic/cytotoxic conditions. Additionally, signalling studies indicated the combination of lipo- and cyto-toxic effects on the muscle cells acted through ceramide, JNK and MAPK pathways and blocking these pathways using PD98059 (MEK inhibitor) and Fumonisin B1 (ceramide inhibitor) significantly reduced levels of cell death. These findings highlight novel pathways associated with in vitro models of lipotoxicity (palmitate-mediated) and cytotoxicity (inflammatory cytokine mediated) in the potential targeting of molecular modulators of sarcopenic obesity.

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  • EPA promotes differentiation by increasing expression of MyoD and Myogenin.

    “Saini and co-workers [135] also show that EPA promotes differentiation by increasing the expression of MyoD and Myogenin.”

    From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [135]

  • EPA combined with palmitate and/or TNF-α treatment during C2 differentiation partially rescues cell death and differentiation via suppression of MAPK.

    “EPA combined with palmitate and/or TNF-α treatment during C2 differentiation partially rescues cell death and differentiation via the suppression of MAPK [135].”

    From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [135]

  • MAPKs can initiate cell death responses in the face of noxious stimuli such as palmitate and TNF-α.

    “Aside from regulating proliferation and differentiation, MAPKs can also initiate cell death responses in the face of noxious stimuli, such as palmitate and TNF-α [134,135].”

    From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [135]

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Authors
Saini, A., Sharples, A. P., Al-Shanti, N., & Stewart, C. E.
Affiliations
  • Karolinska University Hospital (SE)
  • Liverpool John Moores University (GB)
Corresponding author
Sharples, Adam P.
ORCID
Venue
Biogerontology
Publisher
Springer Science and Business Media LLC
Published
2016-11-18
Volume
18
Issue
1
Pages
109-129
ISSN
  • 1389-5729 (ISSN-L)
  • 1573-6768
DOI
10.1007/s10522-016-9667-3
PMC
PMC5288450
OpenAlex
W2552090274
Cited by
53
References
71
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 3 · 2021: 5 · 2020: 12 · 2019: 6 · 2018: 5 · 2017: 2
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Biogerontology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Liverpool John Moores University (acceptedVersion)
  • e-space (Manchester Metropolitan University) (submittedVersion)
  • Keele Research Repository (Keele University) (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Meat and Animal Product Quality
Keywords
eicosapentaenoic acid, omega-3 fatty acids, sarcopenic obesity, palmitate, lipotoxicity, TNF-α, skeletal muscle differentiation, myotube formation, apoptosis, caspase inhibition, ID3, MAPK signaling, ceramide, JNK signaling, inflammation, MyoD, myogenin, insulin-like growth factor II, IGFBP-5
MeSH terms
Animals, Cell Line, Myositis, Palmitates, Regeneration, Tumor Necrosis Factor-alpha, Eicosapentaenoic Acid, Apoptosis, Myoblasts, Mice

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