Sea cucumber female gonad peptides improve bone metabolism in postmenopausal osteoporosis mice by activating muscle AMPK/FNDC5 signaling mediated irisin secretion

• SCGPs inhibited the degeneration of the bone microarchitecture and decreased bone loss in ovariectomized mice. • SCGPs inhibited the OPG/RANKL/NF-κB signaling pathway to reduce bone loss, and promoted the BMP2/Smad signaling pathway to increase bone formation. • SCGPs promoted the secretion of muscle factor irisin through mediating the AMPK/PGC-1 α/FNDC5 signaling pathway. Sea cucumber gonads are protein-balanced by-products rich in glutamate (Glu), glycine (Gly) and aspartate (Asp), which obtained from the procession of sea cucumber. Studies have reported that glutamate and branched-chain amino acids have osteogenic properties and could promote the irisin levels in skeletal muscle. However, the function and mechanism of sea cucumber gonads peptides (SCGPs) to improve bone health remain unknown. In this study, low molecular weight peptides from sea cucumber gonads were obtained and administrated orally to ovariectomized (OVX) mice to investigate the osteogenic activity in vivo . The results showed that SCGPs improved the bone microarchitecture, promoted the bone structural performance and mineral accumulation in a dose-dependent manner (100, 200 mg/kg BW). The immunohistochemical results showed that SCGPs reduced the levels of bone resorption markers and bone formation markers, reversing the high bone turnover state in OVX mice. Mechanistically, SCGPs promoted the secretion of muscle factor irisin through mediating the AMPK/PGC-1α/FNDC5 signaling pathway, thereby inhibiting OPG/RANKL/NF-κB signaling to reduce bone loss, and promoting BMP2/Smad signaling to increase bone formation. These findings collectively suggest that SCGPs exhibits promising potential as a functional food ingredient for the prevention and management of osteoporosis.