Glycosylated Oyster Peptide (GUF3) Enhances Hypolipidemic Activity and Stability for Hyperlipidemia Management

Bioactive peptides derived from natural sources like oysters hold promise for health applications, including managing hyperlipidemia. However, their widespread use in functional foods is often hampered by poor stability, low solubility, and susceptibility to digestive degradation. These limitations reduce their bioavailability and efficacy, necessitating strategies to enhance their physicochemical properties and biological activity. Glycosylation, the enzymatic attachment of sugar moieties, offers a robust method to overcome these challenges by modifying peptide structure and improving resistance to harsh physiological conditions, thereby unlocking their full therapeutic potential.

This study utilized transglutaminase (TGase)-catalyzed glycosylation to conjugate glucosamine (GlcN) with an oyster peptide ultrafiltration fraction (UF3). The resulting glycosylated product, GUF3, was then comprehensively characterized against the unmodified UF3. Researchers evaluated structural changes using techniques like circular dichroism and scanning electron microscopy, alongside physicochemical properties such as particle size, surface hydrophobicity, solubility, and thermal stability. In vitro hypolipidemic activity was assessed by measuring inhibitory effects on pancreatic lipase and cholesterol esterase, both before and after simulated gastrointestinal digestion. Finally, the ability of GUF3 to reduce lipid accumulation, total cholesterol, and triglycerides was tested in free fatty acids-induced HepG2 cells.

Glycosylation significantly altered the oyster peptide's structure, inducing a β-sheet to α-helix shift and transforming its microstructure into a smooth, thin-film network. These structural modifications led to improved physicochemical properties: the average particle size was reduced, surface hydrophobicity lowered, and both solubility and thermal stability were enhanced. Critically, GUF3 demonstrated superior biological activity compared to UF3. It exhibited improved inhibitory activities against pancreatic lipase and cholesterol esterase, key enzymes in lipid digestion. Moreover, GUF3 showed enhanced gastrointestinal resistance, retaining significantly higher enzyme inhibition after simulated intestinal digestion than UF3. In free fatty acids-induced HepG2 cells, GUF3 more effectively reduced lipid accumulation, total cholesterol, and triglycerides, indicating its potent cellular hypolipidemic effects. This suggests a direct impact on cellular lipid metabolism.

The glycosylated oyster peptide (GUF3) demonstrated superior gastrointestinal resistance, maintaining higher enzyme inhibition post-digestion compared to its unmodified counterpart, indicating enhanced stability and bioavailability.