Lipid remodelling and an altered membrane proteome may drive the effects of EPA and DHA treatment on skeletal muscle glucose uptake and protein accretion

Stewart Jeromson, Ivor Mackenzie, Mary K. Doherty, Phillip D. Whitfield, Gordon Bell, James Dick, Andy Shaw, Francesco Rao, Stephen Ashcroft, Andrew Philp, Stuart Galloway, Iain Gallagher, D. Lee Hamilton (Lead / Corresponding author)

Research output: Contribution to journalArticle

12 Citations (Scopus)
158 Downloads (Pure)

Abstract

In striated muscle, EPA and 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 C2C12 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 on the impact of treating CM with EPA and DHA on lipidomic and proteomic profiles. FAME analysis revealed that both EPA and DHA led to similar but substantial changes in fatty acid profiles. 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 5 (EPA treatment) or 6 (DHA treatment) double bonds. As these are typically membrane associated lipid species we hypothesized that these treatments differentially altered the membrane-associated proteome. 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 remodelling induced by EPA treatment.

Original languageEnglish
Article number00438
Pages (from-to)e605-e619
Number of pages15
JournalAmerican Journal of Physiology, Endocrinology and Metabolism
Volume314
Early online date27 Jun 2017
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • Cell signalling
  • Fish oil
  • Fatty acid
  • Insulin
  • Lipidomics
  • Lipids

Fingerprint Dive into the research topics of 'Lipid remodelling and an altered membrane proteome may drive the effects of EPA and DHA treatment on skeletal muscle glucose uptake and protein accretion'. Together they form a unique fingerprint.

  • Cite this

    Jeromson, S., Mackenzie, I., Doherty, M. K., Whitfield, P. D., Bell, G., Dick, J., Shaw, A., Rao, F., Ashcroft, S., Philp, A., Galloway, S., Gallagher, I., & Hamilton, D. L. (2018). Lipid remodelling and an altered membrane proteome may drive the effects of EPA and DHA treatment on skeletal muscle glucose uptake and protein accretion. American Journal of Physiology, Endocrinology and Metabolism, 314, e605-e619. [00438]. https://doi.org/10.1152/ajpendo.00438.2015