Dietary long-chainn-3 fatty acids modify blood and cardiac phospholipids and reduce protein kinase-C-δ and protein kinase-C-ε translocation

Abstract

The effects of an n-3 PUFA-enriched diet on cardiac cell membrane phospholipid fraction compositions and associated protein kinase-C (PKC) translocation modification have never been studied in higher mammals. This is of importance since membrane fatty acid composition has been shown to influence PKC signalling pathways. In the present study, we have tested whether the incorporation of n-3 PUFA in cardiac membrane phospholipids correlated with changes in the fatty acid composition of diacylglycerols (DAG) and led to a differential translocation of PKC isoforms. Two groups of five dogs were fed the standard diet supplemented with palm oil or fish oil for 8 weeks. Dogs fed a fish oil-enriched diet showed a preferential incorporation of EPA and, to a lesser extent, of DHA, at the expense of arachidonic acid, in the circulating TAG, plasma phospholipids, erythrocyte phospholipids and cardiomyocyte phospholipid fractions. Analysis of 1,2-DAG fatty acid composition also indicated a preferential enrichment of EPA compared with DHA. Associated with these results, a reduction in the expression of PKC-δ and PKC-ε isoforms in the particulate fractions was observed whereas no effect was seen for PKC-α and PKC-ζ. We conclude that a fish oil-enriched diet induces a modification in fatty acid composition of cardiac membrane phospholipids, associated with a differential translocation of PKC isoforms. These results can be explained by the production of structurally different DAG that may participate in some of the protective effects of n-3 PUFA against various chronic diseases.

Fatty acid patterns of dog erythrocyte membranes after feeding of a fish-oil based DHA-rich supplement with a base diet low in n-3 fatty acids versus a diet containing added n-3 fatty acids

“…A preferential incorporation of EPA was also observed in humans receiving a EPA-rich fish oil diet[32]. Our data also contradict the results of Jude et al[33] in dogs. In this study a fish oil-enriched diet containing twice as much DHA as EPA showed a preferential incorporation of EPA.…”

“…The incorporation of n-3 FA at the expense of AA has been shown earlier by Jude et al[33] and Kew et al[26]. There was also a significant reduction of n-6 FA in FO, despite the fact, that the daily uptake of n-6 FA in this group (787.5 mg/d/kg body weight) was higher than in ADD (533.4 mg/d/kg body weight).…”

Regulatory activity of polyunsaturated fatty acids in T-cell signaling

“…Since SDG and SEG in the absence or presence of SAG differentially modulated PKC isoforms, it appeared that there might be two types of binding sites for DAG species which, in the presence of PS and calcium, might signal differently. These data suggest that the actions of DAG species on PKC activation are complex and may exert both inhibitory and stimulatory effects [75, 76]. In dogs fed a fish oil diet, DAG containing n-3 PUFA were associated with a reduction in the expression of PKC-δ and PKC-ε isoforms [76].…”

Comparison of docosahexaenoic acid uptake in murine cardiomyocyte culture and tissue: Significance to physiologically relevant studies

“…One potential explanation is that DHA inhibits sPLA 2 via ERK and PKC, as previously shown in human endothelial cells [12]. Reductions in the expression of PKC-δ and PKC-ε isoforms have also been reported in cardiomyocytes isolated from dogs fed fish oil [20]. Hence, despite an increased availability of ARA, the overall effect of DHA supplementation is conducive to lower production of inflammatory mediators.…”