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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Molecular Science of Eicosapentaenoic Acid (EPA) Omega-3 Fatty Acid Using Nannochloropsis oceanica as a Model Organism

5 affiliations
  1. 1School of Agriculture and Food Sustainability, University of Queensland, St Lucia, QLD 4072, Australia
  2. 2Algemy Pty Ltd., Brisbane, QLD 4035, Australia
  3. 3Advantage Plants Consulting Pty Ltd., Brisbane, QLD 4500, Australia
  4. 4SeoO2 Pty Ltd.,Rozelle, NSW 2039, Australia
  5. 5Faculty of Science and Engineering, Southern Cross University, Military Road, P.O. Box 157, East Lismore, NSW 2480, Australia

Abstract

The EPA-rich marine microalga Nannochloropsis oceanica provides insight into EPA biosynthesis via the characterized Δ6-desaturase pathway, positioning this microalga for both experimental research and sustainable production solutions for non-fish oil-derived EPA oils. This review constructs a comprehensive molecular-to-clinical framework demonstrating how the chemical structure of eicosapentaenoic acid (EPA) determines its biological activities, i.e., the specific positioning of the Δ17 double bond governs competitive enzymatic metabolism with arachidonic acid (ARA), yielding attenuated 3-series and 5-series eicosanoids while uniquely enabling E-series resolvin biosynthesis. Metabolic pathway modulation (AMPK, NF-κB, and SREBP-1c) translate biochemical events into transcriptional reprogramming. Sustained alterations in gene expression, membrane composition, and inflammatory mediator profiles manifest as clinical benefits across cardiovascular disease, metabolic disorders, inflammatory conditions, and psychiatric illnesses. The pleiotropic nature of EPA effectssimultaneously anti-inflammatory, TAG-lowering, anti-arrhythmic, insulin-sensitizing, and pro-resolving — arises not from independent mechanisms but from coordinated, multi-level integration. The ARA:EPA ratio emerges as the unifying quantitative biomarker, integrating dietary intake, competitive membrane incorporation, eicosanoid biosynthetic balance, and tissue-level inflammatory tone into a single metric predictive of disease risk and therapeutic response. Lowering this ratio through EPA supplementation represents a systems-level intervention: simultaneously reducing pro-inflammatory mediator production, enhancing resolution capacity, improving metabolic flexibility, and stabilizing cellular energetics.

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BibTeX
@article{stephens2026molecular,
  title = {{Molecular Science of Eicosapentaenoic Acid (EPA) Omega-3 Fatty Acid Using Nannochloropsis oceanica as a Model Organism}},
  author = {Evan D. Stephens and Skye Thomas-Hall and Victor Joseph Galea and Kirsten Heimann},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = nov,
  doi = {10.3390/ijms27219834},
  url = {https://www.mdpi.com/1422-0067/27/21/9834},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Molecular Science of Eicosapentaenoic Acid (EPA) Omega-3 Fatty Acid Using Nannochloropsis oceanica as a Model Organism
AU  - Evan D. Stephens
AU  - Skye Thomas-Hall
AU  - Victor Joseph Galea
AU  - Kirsten Heimann
PY  - 2026
DA  - 2026/11/02
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219834
UR  - https://www.mdpi.com/1422-0067/27/21/9834
AB  - The EPA-rich marine microalga Nannochloropsis oceanica provides insight into EPA biosynthesis via the characterized Δ6-desaturase pathway, positioning this microalga for both experimental research and sustainable production solutions for non-fish oil-derived EPA oils. This review constructs a comprehensive molecular-to-clinical framework demonstrating how the chemical structure of eicosapentaenoic acid (EPA) determines its biological activities, i.e., the specific positioning of the Δ17 double bond governs competitive enzymatic metabolism with arachidonic acid (ARA), yielding attenuated 3-series and 5-series eicosanoids while uniquely enabling E-series resolvin biosynthesis. Metabolic pathway modulation (AMPK, NF-κB, and SREBP-1c) translate biochemical events into transcriptional reprogramming. Sustained alterations in gene expression, membrane composition, and inflammatory mediator profiles manifest as clinical benefits across cardiovascular disease, metabolic disorders, inflammatory conditions, and psychiatric illnesses. The pleiotropic nature of EPA effectssimultaneously anti-inflammatory, TAG-lowering, anti-arrhythmic, insulin-sensitizing, and pro-resolving — arises not from independent mechanisms but from coordinated, multi-level integration. The ARA:EPA ratio emerges as the unifying quantitative biomarker, integrating dietary intake, competitive membrane incorporation, eicosanoid biosynthetic balance, and tissue-level inflammatory tone into a single metric predictive of disease risk and therapeutic response. Lowering this ratio through EPA supplementation represents a systems-level intervention: simultaneously reducing pro-inflammatory mediator production, enhancing resolution capacity, improving metabolic flexibility, and stabilizing cellular energetics.
SN  - 1422-0067
ER  -