Flax lignans regulate the conversion of <i>α</i>-linolenic acid into <i>n</i>-3 LCPUFAs in mice ingesting sunflower phospholipid-stabilized nanoemulsions

Dietary supplementation with plant-derived α-linolenic acid (ALA) has the potential to alleviate the insufficient intake of global n-3 long-chain unsaturated fatty acids (n-3 LCPUFAs), but faces the bottleneck of high β-oxidation consumption, oxidative susceptibility, and low conversion efficiency. The current study investigated how flax lignans with different degrees of polymerization and glycosylation affect the conversion of ALA to n-3 LCPUFAs in mice over 35 days of administering sunflower phospholipid-stabilized flaxseed oil nanoemulsions. Results showed that flax lignan macromolecules (FLM) increased hepatic protein expression of elongase of very long chain fatty acid 5 (Elovl5, +24.2%) and fatty acid desaturase 2 (Fads2, +44.7%), thereby positively regulating ALA conversion pathways and raising serum eicosapentaenoic acid (EPA) levels (+52%) via liver lipid re-efflux. Secoisolariciresinol diglucoside (SDG) enhanced ALA desaturation by upregulating hepatic protein expression of Fads1 (+30.4%) and Fads2 (+45.6%), increasing serum EPA levels (+56%) and hepatic docosahexaenoic acid (DHA) levels (+10%). Secoisolariciresinol (SECO) elevated hepatic protein expression of Elovl2 (+30.7%), Elovl5 (+11.7%), Fads1 (+37.9%), and Fads2 (+24.1%), but also increased carnitine palmitoyltransferase 1a (Cpt1a, +45.2%), leading to decreased ALA, EPA, and DHA levels in serum and liver. Therefore, in comparison, FLM and SDG emerge as the dominant structural units that positively regulate the conversion of ALA. These findings lay a groundwork for designing precise dietary delivery systems to enhance the conversion to n-3 LCPUFAs.