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EPA, DHA, and Lipoic Acid Differentially Modulate the n-3 Fatty Acid Biosynthetic Pathway in Atlantic Salmon Hepatocytes

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Lipids

Abstract

The aim of the present study was to investigate how EPA, DHA, and lipoic acid (LA) influence the different metabolic steps in the n-3 fatty acid (FA) biosynthetic pathway in hepatocytes from Atlantic salmon fed four dietary levels (0, 0.5, 1.0 and 2.0%) of EPA, DHA or a 1:1 mixture of these FA. The hepatocytes were incubated with [1-14C] 18:3n-3 in the presence or absence of LA (0.2 mM). Increased endogenous levels of EPA and/or DHA and LA exposure both led to similar responses in cells with reduced desaturation and elongation of [1-14C] 18:3n-3 to 18:4n-3, 20:4n-3, and EPA, in agreement with reduced expression of the Δ6 desaturase gene involved in the first step of conversion. DHA production, on the other hand, was maintained even in groups with high endogenous levels of DHA, possibly due to a more complex regulation of this last step in the n-3 metabolic pathway. Inhibition of the Δ6 desaturase pathway led to increased direct elongation to 20:3n-3 by both DHA and LA. Possibly the route by 20:3n-3 and then Δ8 desaturation to 20:4n-3, bypassing the first Δ6 desaturase step, can partly explain the maintained or even increased levels of DHA production. LA increased DHA production in the phospholipid fraction of hepatocytes isolated from fish fed 0 and 0.5% EPA and/or DHA, indicating that LA has the potential to further increase the production of this health-beneficial FA in fish fed diets with low levels of EPA and/or DHA.

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Abbreviations

ASP:

Acid-soluble products

CE:

Cholesteryl esters

DHA:

Docosahexaenoic acid (22:6n-3)

EPA:

Eicosapentaenoic acid (20:5n-3)

FO:

Fish oil

LA:

Lipoic acid

MDG:

Monoacylglycerols and diacylglycerols

NL:

Neutral lipids

PL:

Phospholipids

PUFA:

Polyunsaturated fatty acid(s)

TAG:

Triacylglycerol(s)

LC-PUFA:

Long chain polyunsaturated fatty acid(s)

VO:

Vegetable oil

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Acknowledgements

The authors would like to thank Målfrid Tofteberg Bjerke and Inger Øien Kristiansen for their skilful technical assistance. This work was carried out with support from the Norwegian Research Council (Grant Number NFR 224913).

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Authors and Affiliations

  1. Nofima (Norwegian Institute of Food, Fisheries and Aquaculture Research), P.O. Box 210, 1431, Ås, Norway

    Marta Bou, Tone-Kari Østbye & Bente Ruyter

  2. Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, Ås, Norway

    Marta Bou & Bente Ruyter

  3. Nofima, 6600, Sunndalsøra, Norway

    Gerd M. Berge

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  1. Marta Bou
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  2. Tone-Kari Østbye
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Bou, M., Østbye, TK., Berge, G.M. et al. EPA, DHA, and Lipoic Acid Differentially Modulate the n-3 Fatty Acid Biosynthetic Pathway in Atlantic Salmon Hepatocytes. Lipids 52, 265–283 (2017). https://doi.org/10.1007/s11745-017-4234-5

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