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

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. 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-C-13]glucose) and amino acids ([1-C-13]phenylalanine), blood samples were collected to assess glucose and phenylalanine kinetics. Soleus and longissimus dorsi muscles were extracted for protein and mRNA analyses. 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 gamma (PP2A-B56-gamma), forkhead box containing proteins O-subclass 3a (FOX03a)([Ser253]) or inflammatory markers (Interleukin-6, Interleukin-1 beta, tumour necrosis factor-alpha, and cyclooxygenase-2). Our data suggest that the fish oil may stimulate endogenous glucose production and increase anabolic signalling in ageing rats.