Duck Egg White–Derived Peptide VSEE (Val‐Ser‐Glu‐Glu) Regulates Bone and Lipid Metabolisms by Wnt/β‐Catenin Signaling Pathway and Intestinal Microbiota

Scope Val‐Ser‐Glu‐Glu (VSEE), identified from duck egg white peptides, has been proven to facilitate calcium absorption in a previous study. Since prevention of osteoporosis is important, it might act as a potential cofactor in osteoporosis prevention. Therefore, the aim of this study is to investigate the regulation of VSEE on osteoporosis and abnormal lipid metabolisms. Methods and results MC3T3‐E1 cell and ovariectomized (OVX) rat model are used to evaluate VSEE on regulation of bone and lipid metabolisms. Differentiation and matrix mineralization of preosteoblast are significantly increased by VSEE ( p <0.05), which attributed to stimulating calcium influx, then to activating Wnt/β‐catenin signaling pathway and regulating runt‐related transcription factor 2 and osteoprotegerin. VSEE can cross Caco‐2/HT‐29 co‐cultured monolayer via paracellular pathway and peptide transporter 1 (PepT1), and can be detected in blood and maximum concentration is 122.84 ± 3.68 mg L −1 at 60 min. Additionally, VSEE reverses bone loss and regulate dyslipidemia through Wnt/β‐catenin signaling pathway in OVX rats. Firmicutes phylum, Veillonellaceae, Prevotellaceae and six genera in VSEE group are significantly different compared with the Model group ( p < 0.05). Conclusion VSEE promotes bone growth and inhibit abnormal lipid metabolism in an OVX model through the regulation of intestinal microbiota compositions and Wnt/β‐catenin signal pathway.