Lipid remodeling and an altered membrane-associated proteome may drive the differential effects of EPA and DHA treatment on skeletal muscle glucose uptake and protein accretion
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In striated muscle, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have differential effects on the metabolism of glucose and differential effects on the metabolism of protein. We have shown that, despite similar incorporation, treatment of C 2 C 12 myotubes (CM) with EPA but not DHA improves glucose uptake and protein accretion. We hypothesized that these differential effects of EPA and DHA may be due to divergent shifts in lipidomic profiles leading to altered proteomic profiles. We therefore carried out an assessment of the impact of treating CM with EPA and DHA on lipidomic and proteomic profiles. Fatty acid methyl esters (FAME) analysis revealed that both EPA and DHA led to similar but substantials changes in fatty acid profiles with the exception of arachidonic acid, which was decreased only by DHA, and docosapentanoic acid (DPA), which was increased only by EPA treatment. Global lipidomic analysis showed that EPA and DHA induced large alterations in the cellular lipid profiles and in particular, the phospholipid classes. Subsequent targeted analysis confirmed that the most differentially regulated species were phosphatidylcholines and phosphatidylethanolamines containing long-chain fatty acids with five (EPA treatment) or six (DHA treatment) double bonds. As these are typically membrane-associated lipid species we hypothesized that these treatments differentially altered the membrane-associated proteome. Stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics of the membrane fraction revealed significant divergence in the effects of EPA and DHA on the membrane-associated proteome. We conclude that the EPA-specific increase in polyunsaturated long-chain fatty acids in the phospholipid fraction is associated with an altered membrane-associated proteome and these may be critical events in the metabolic remodeling induced by EPA treatment.
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The potential positive effects of n-3 PUFAs on myogenesis may relate to their capacity to alter cell membrane lipid composition, changing the profile of membrane-bound proteins of lipid rafts.
“The potential positive effects of n-3 PUFA’s on myogenesis may relate to their capacity to alter the cell membrane lipid composition, which in turn, changes the profile of membrane bound proteins of lipid rafts [79,80].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [80]
In isolation, n-3 PUFAs do not appear to have any effect on the mTOR signalling pathway in fully formed C2C12 cells.
“In isolation, n-3 PUFAs do not appear to have any effect on mTOR signalling pathway in fully formed C2C12 cells [80].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [80]
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- Authors
- Jeromson, S., Mackenzie, I., Doherty, M. K., Whitfield, P. D., Bell, G., Dick, J., Shaw, A., Rao, F. V., Ashcroft, S. P., Philp, A., Galloway, S. D. R., Gallagher, I., & Hamilton, D. L.
- Affiliations
- University of Stirling (GB)
- University of the Highlands and Islands (GB)
- DC Biosciences, Limited, Dundee Technopole, Dundee, United Kingdom
- University of Birmingham (GB)
- Corresponding author
- Hamilton, D. Lee
- ORCID
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2018-06-01
- Volume
- 314
- Issue
- 6
- Pages
- E605-E619
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2730269751
- Cited by
- 40
- References
- 57
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 1
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, other-oa)
- Own your potential (DEAKIN) (submittedVersion)
- Stirling Online Research Repository (University of Stirling) (submittedVersion, public-domain)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- eicosapentaenoic acid, docosahexaenoic acid, omega-3 fatty acids, skeletal muscle, myotubes, lipid remodeling, phospholipids, phosphatidylcholine, phosphatidylethanolamine, docosapentaenoic acid, arachidonic acid, glucose uptake, muscle protein accretion, fatty acid methyl esters, long-chain polyunsaturated fatty acids
- MeSH terms
- Animals, Cell Membrane, Cells, Cultured, Docosahexaenoic Acids, Fatty Acids, Glucose, Membrane Proteins, Triglycerides, Eicosapentaenoic Acid, Muscle, Skeletal, Proteome, Carbohydrate Metabolism, Lipid Metabolism, Mice
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