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

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-(13)C]glucose) and amino acids ([1-(13)C]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.