Abstract
This study explores the effect of high dietary arachidonic acid (ARA) levels (high ARA) compared with low dietary ARA levels (control) on the general metabolism using zebrafish as the model organism. The fatty acid composition of today's 'modern diet' tends towards higher n-6 PUFA levels in relation to n-3 PUFA. Low dietary n-3:n-6 PUFA ratio is a health concern, as n-6 PUFA give rise to eicosanoids and PG, which are traditionally considered pro-inflammatory, especially when derived from ARA. Juvenile zebrafish fed a high-ARA diet for 17 d had a lower whole-body n-3:n-6 PUFA ratio compared with zebrafish fed a low-ARA (control) diet (0·6 in the control group v. 0·2 in the high-ARA group). Metabolic profiling revealed altered levels of eicosanoids, PUFA, dicarboxylic acids and complex lipids such as glycerophospholipids and lysophospholipids as the most significant differences compared with the control group. ARA-derived hydroxylated eicosanoids, such as hydroxy-eicosatetraenoic acids, were elevated in response to high-ARA feed. In addition, increased levels of oxidised lipids and amino acids indicated an oxidised environment due to n-6 PUFA excess in the fish. To conclude, our results indicate that an ARA-enriched diet induces changes in complex lipids and immune-related eicosanoids and increases levels of oxidised lipids and amino acids, suggesting oxidative stress and lipid peroxidation.
Highlights
This study explores the effect of high dietary arachidonic acid (ARA) levels compared with low dietary ARA levels on the general metabolism using zebrafish as the model organism
Powell et al[44] investigated the role of ARA and different dietary n-3:n-6 PUFA ratios in inflammation in zebrafish. They measured key inflammatory markers, growth and body fat in adult zebrafish in response to dietary n-3:n-6 PUFA ratios. These results indicate that a low n-3:n-6 PUFA ratio can impact health through metabolic changes when high levels of ARA are provided through diet
We found that high ARA levels contribute to a strong shift in lipid metabolism involving significant lipid mediators, which suggests an impact on physiological functions and challenges the redox environment in the fish
Summary
This study explores the effect of high dietary arachidonic acid (ARA) levels (high ARA) compared with low dietary ARA levels (control) on the general metabolism using zebrafish as the model organism. Oxylipin and ARA levels can be influenced by the diet directly; ARA conversion to eicosanoids is a rate-limiting enzymatic process[12] Biological functions of those oxylipins, and especially eicosanoids, are traditionally considered anti-inflammatory when derived from n-3 PUFA and pro-inflammatory when derived from n-6 PUFA. ARA-derived eicosanoids have been studied intensively, and ARA is widely discussed in the context of signalling cascades regulating inflammation, pain, fever and other homoeostatic actions such as blood pressure, bone metabolism, growth and reproduction[19,20,21,22,23] These biological functions are traditionally attributed to the immunomodulating lipid mediators such as ARA-derived hydroxy-eicosatetraenoic acids (HETE)(24), PG, thromboxanes and leukotrienes[6,15]. These nuclear receptors are regulated by direct fatty acid- and eicosanoid-binding, or by the regulation of G-protein-linked cell surface receptors, thereby activating signalling cascades[24,26,27,28]
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