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)

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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
JournalAmerican Journal of Physiology, Endocrinology and Metabolism
Early online date27 Jun 2017
DOIs
Publication statusE-pub ahead of print - 27 Jun 2017

Fingerprint

Proteome
Skeletal Muscle
Proteomics
Lipids
Glucose
Fatty Acids
Membranes
Skeletal Muscle Fibers
Phospholipids
Proteins
Phosphatidylethanolamines
Striated Muscle
Membrane Lipids
Phosphatidylcholines

Keywords

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

Cite this

Jeromson, Stewart ; Mackenzie, Ivor ; Doherty, Mary K. ; Whitfield, Phillip D. ; Bell, Gordon ; Dick, James ; Shaw, Andy ; Rao, Francesco ; Ashcroft, Stephen ; Philp, Andrew ; Galloway, Stuart ; Gallagher, Iain ; Hamilton, D. Lee. / Lipid remodelling and an altered membrane proteome may drive the effects of EPA and DHA treatment on skeletal muscle glucose uptake and protein accretion. In: American Journal of Physiology, Endocrinology and Metabolism. 2017.
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title = "Lipid remodelling and an altered membrane proteome may drive the effects of EPA and DHA treatment on skeletal muscle glucose uptake and protein accretion",
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.",
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author = "Stewart Jeromson and Ivor Mackenzie and Doherty, {Mary K.} and Whitfield, {Phillip D.} and Gordon Bell and James Dick and Andy Shaw and Francesco Rao and Stephen Ashcroft and Andrew Philp and Stuart Galloway and Iain Gallagher and Hamilton, {D. Lee}",
note = "This work was funded by a University of Stirling capital investment award (DLH) and Society for Endocrinology and American College of Sports Medicine early career awards (DLH). The financial support of Highlands and Islands Enterprise, Scottish Funding Council and European Regional Development Fund is gratefully acknowledged (IM, MKD and PDW). We acknowledge Liz Mackinlay for assistance with the FAME analysis.",
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Lipid remodelling and an altered membrane proteome may drive the effects of EPA and DHA treatment on skeletal muscle glucose uptake and protein accretion. / Jeromson, Stewart; Mackenzie, Ivor; Doherty, Mary K.; Whitfield, Phillip D.; Bell, Gordon; Dick, James; Shaw, Andy; Rao, Francesco; Ashcroft, Stephen; Philp, Andrew; Galloway, Stuart; Gallagher, Iain ; Hamilton, D. Lee (Lead / Corresponding author).

In: American Journal of Physiology, Endocrinology and Metabolism, 27.06.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lipid remodelling and an altered membrane proteome may drive the effects of EPA and DHA treatment on skeletal muscle glucose uptake and protein accretion

AU - Jeromson, Stewart

AU - Mackenzie, Ivor

AU - Doherty, Mary K.

AU - Whitfield, Phillip D.

AU - Bell, Gordon

AU - Dick, James

AU - Shaw, Andy

AU - Rao, Francesco

AU - Ashcroft, Stephen

AU - Philp, Andrew

AU - Galloway, Stuart

AU - Gallagher, Iain

AU - Hamilton, D. Lee

N1 - This work was funded by a University of Stirling capital investment award (DLH) and Society for Endocrinology and American College of Sports Medicine early career awards (DLH). The financial support of Highlands and Islands Enterprise, Scottish Funding Council and European Regional Development Fund is gratefully acknowledged (IM, MKD and PDW). We acknowledge Liz Mackinlay for assistance with the FAME analysis.

PY - 2017/6/27

Y1 - 2017/6/27

N2 - 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.

AB - 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.

KW - Cell signalling

KW - Fish oil

KW - Fatty acid

KW - Insulin

KW - Lipidomics

KW - Lipids

U2 - 10.1152/ajpendo.00438.2015

DO - 10.1152/ajpendo.00438.2015

M3 - Article

JO - American Journal of Physiology, Endocrinology and Metabolism

JF - American Journal of Physiology, Endocrinology and Metabolism

SN - 0193-1849

ER -