A Schizochytrium sp.-derived lipid-lowering peptide: Optimized enzymatic production, sequence identification, and action mechanism

The global rise in unhealthy lifestyles has accelerated hyperlipidemia prevalence, increasing demand for natural lipid-lowering agents as alternatives to conventional pharmaceuticals. This study investigated defatted Schizochytrium sp. biomass as a potential source of these bioactive compounds. Schizochytrium sp. proteins were enzymatically hydrolyzed under response surface methodology (RSM)-optimized conditions: 3.90 % (w/v) substrate, 9.60 % (w/w) enzyme, 45 °C, 4 h. The <3 kDa ultrafiltrate exhibited 57.38 % pancreatic lipase inhibition. Liquid chromatography-mass spectrometry (LC-MS/MS) identified VIEIPDDVAEK (VIE-11) as the core peptide with potent activity (IC 50  = 5.10 μM), supported by molecular docking studies. Structural characterization revealed predominantly α-helical and random coil conformations with hydrophobic residues. In free fatty acids (FFA)-induced HepG2 cells modeling hepatic steatosis, VIE-11 (50, 100, and 200 μM) reduced intracellular lipid accumulation, and was associated with downregulation of lipogenic regulators (SREBP-1c, FAS, CD36) and upregulation of lipid catabolism and export markers (ATGL, PPARα, CPT1A, APOB, MTTP). These findings suggest that VIE-11 may hold potential as a nutraceutical candidate for hyperlipidemia intervention.