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European Journal of Nutrition

, Volume 52, Issue 2, pp 647–657 | Cite as

Fish oil positively regulates anabolic signalling alongside an increase in whole-body gluconeogenesis in ageing skeletal muscle

  • Torkamol Kamolrat
  • Stuart R. GrayEmail author
  • M. Carole Thivierge
Original Contribution

Abstract

Purpose

Fish oil, containing mainly long-chain n-3 polyunsaturated fatty acids (LCn-3PUFA), has been found to acutely stimulate protein synthesis and insulin-mediated glucose metabolism. However, the underlying mechanism and more prolonged effect of fish oil during ageing remain to be determined.

Methods

Fish oil (EPAX6000; 49.6 % eicosapentaenoic acid, 50.4 % docosahexaenoic acid) or control oil (60 % olive, 40 % soy) supplementation was delivered, via chocolate-derived sweets, to rats for 8 weeks. Throughout the study, food intake and body weight were recorded and body composition was investigated using EchoMRI. During the last 40 min of a 6 h infusion, with labelled dextrose ([U-13C]glucose) and amino acids ([1-13C]phenylalanine), blood samples were collected to assess glucose and phenylalanine kinetics. Soleus and longissimus dorsi muscles were extracted for protein and mRNA analyses.

Results

Fish oil had no effect on food intake or body composition. An increased whole-body glucose turnover, mainly accounted for via an increase in endogenous glucose production, was observed with fish oil feeding. No effects on whole-body phenylalanine turnover were observed. In longissimus dorsi, fish oil augmented the phosphorylation of phosphoinositide 3-kinase (PI3K)[Tyr458] (P = 0.04) and 70 kDa ribosomal protein S6 kinase (p70s6k)[Thr389] (P = 0.04). There were no differences in protein kinase B (Akt)[Ser473], mammalian target of rapamycin (mTOR)[Ser2448], protein phosphatase 2A (PP2A) 56 kDa regulatory B subunit γ (PP2A-B56-γ), forkhead box containing proteins O-subclass 3a (FOX03a)[Ser253] or inflammatory markers (Interleukin-6, Interleukin-1 β, tumour necrosis factor-α, and cyclooxygenase-2).

Conclusions

Our data suggest that the fish oil may stimulate endogenous glucose production and increase anabolic signalling in ageing rats.

Keywords

Ageing Fish oil p70s6k Metabolism Insulin sensitivity 

Abbreviations

4EBP1

Eukaryotic initiation factor 4E (eIF4E) binding protein 1

Akt

Protein kinase B

COX2

Cyclooxygenase-2

DHA

Docosahexaenoic acid

EPA

Eicosapentaenoic acid

FoxO3a

Forkhead box containing proteins, O-subclass 3a

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

GNG

Gluconeogenesis

IL-1β

Interleukin-1 beta

IL-6

Interleukin-6

LCn-3PUFA

Long-chain n-3 polyunsaturated fatty acids

LD

Longissimus dorsi

MCP1

Monocyte chemotactic protein 1

mTOR

Mammalian target of rapamycin

p70s6k

70 kDa Ribosomal protein S6 kinase

PAI1

Plasminogen activator inhibitor 1

PDK1

Phosphoinositide-dependent protein kinase 1

PI3K

Phosphotidylinositol-3-kinase

PP2A-B56γ

Protein phosphatase 2A (PP2A) 56 kDa regulatory B subunit γ

Ptgs2

Prostaglandin-endoperoxide synthase 2

rps6

Ribosomal protein s6

TNF-α

Tumour necrosis factor alpha

TTR

Tracer to tracee ratio

Notes

Acknowledgments

The authors would like to thank Patricia Crombie, Denise Tosh, Alun Hughes and Cecile Itzstein for technical assistance. Special thanks are extended to A. Graham Calder and Susan Anderson for their great assistance in the GC–MS analyses. Acknowledgements are also extended to Grietje Holtrop for her assistance in performing the deconvolution matrix approach to the glucose isotopomer isotopic enrichment data. The study was funded by the Scottish Executive Environment and Rural Affairs Department. T. K. has been supported by the grant from Ministry of Science and Technology and Khon Kaen University, Thailand.

Conflict of interest

The authors have no conflicts of interest.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Torkamol Kamolrat
    • 1
  • Stuart R. Gray
    • 1
    Email author
  • M. Carole Thivierge
    • 2
  1. 1.Musculoskeletal Research ProgrammeInstitute of Medical Sciences, University of AberdeenAberdeenScotland, UK
  2. 2.Rowett Institute of Nutrition and HealthUniversity of AberdeenAberdeenScotland, UK

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