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

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.