Larimichthys crocea-Derived Calcium-Chelating Peptides Attenuate Leuprorelin-Induced Bone Loss and Lipid Metabolic Alterations in Mice.

Estrogen deficiency induces bone loss and is accompanied by lipid metabolic disturbances. This study investigated the protective effects of Larimichthys crocea-derived calcium-chelating peptides (LCP) in a leuprorelin-induced estrogen-deficient mouse model. LCP attenuated tibial trabecular deterioration, increased serum procollagen type I N-terminal propeptide (PINP), osteocalcin (OCN), and bone-specific alkaline phosphatase (BALP), and reduced C-terminal telopeptide of type I collagen (CTX-I). Histological analyses further showed increased trabecular area and OCN expression and reduced marrow adiposity. LCP also attenuated alterations in serum lipid profiles and circulating levels of leptin and adiponectin, while reducing adipogenesis-related gene expression in femoral tissue and white adipose tissue. Exploratory assays using group-pooled cultures of bone marrow mesenchymal stem cells (BMSCs) showed differentiation-related patterns that were directionally consistent with the in vivo findings, but these descriptive observations require confirmation using independent biological replicates. Correlation analysis revealed associations among bone mass, osteogenesis-related indicators, and lipid metabolism-related parameters. Collectively, LCP attenuated estrogen deficiency-induced bone loss together with favorable changes in indicators related to bone formation, adipogenesis, and lipid metabolism. These findings support further investigation of LCP as a food-derived nutritional ingredient for supporting bone health under estrogen-deficient conditions.