Flax lignan-fortified nanoemulsions potentiate the conversion of α-linolenic acid to n-3 LCPUFAs: cumulative metabolic patterns in non-fasting mice

Abstract

As an essential n-3 fatty acid required by the human body, α-linolenic acid (ALA) can be metabolically converted in vivo into n-3 long chain polyunsaturated fatty acids (LCPUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exhibiting biological functions and resource sustainability, and its conversion may be modulated by specific polyphenols. This study investigated the metabolic conversion profile in non-fasted mice following the intake of flaxseed oil nanoemulsions and assessed the potential regulatory effects of co-ingesting structurally distinct flax lignans. The results showed that co-administration of the flax lignan macromolecule (FLM) increased serum EPA by 31.9%, DHA by 20.2%, and hepatic EPA by 35.1%. Secoisolariciresinol diglucoside (SDG) increased serum EPA by 38% and hepatic EPA by 47.4%. Secoisolariciresinol (SECO) elevated serum EPA by 30.0%, and hepatic EPA, docosapentaenoic acid (DPA), and DHA by 57.9%, 19.7%, and 17.7%, respectively. Lipidomics revealed FLM/SECO enriched ALA-derived phospholipids (e.g., PC 38:7|18:2_20:5), while SDG stimulated EPA/DHA-containing triglycerides (e.g., TG 58:13|18:3_20:5_20:5), indicating lignan-specific effects. Furthermore, in vivo metabolic studies and HepG2 cell experiments indicated that the structural characteristics of flax lignans might determine their material basis of intestinal transport and hepatic metabolism, thereby modulating ALA absorption, transport, and conversion, with the characteristic metabolites SDG and enterodiol (ENL) further promoting downstream ALA-derived products (C20:4n-3, 48.6% or C20:3n-3, 48.1%), highlighting their regulatory roles. This study provides a theoretical foundation for developing functional lipid delivery systems based on lignan structural features and nutritional intervention strategies aimed at enhancing ALA metabolic conversion.