Osteoporosis is a systemic, progressive bone disease that causes metabolic disorders. Previous study identified the preventive effects of hydrolyzed egg yolk peptide (YPEP) on osteoporosis. However, the underlying antiosteoporosis mechanism remains unclear. Herein, 30 female rats were randomly divided into 5 groups (n = 6), including the sham, OVX, E2 (25 μg/kg/d 17β-estradiol), LYPEP (10 mg/kg/d YPEP), and HYPEP (40 mg/kg/d YPEP) groups. YPEP treatment significantly changed bone turnover marker levels and prevented the deterioration of bone structure and strength caused by ovariectomy. YPEP supplementation significantly changed endogenous metabolites related to lipid metabolism in the serum of ovariectomized rats, identifying 46 metabolites closely linked to bone biomarkers. Additionally, YPEP reduced the expression of the lipid metabolism-related protein peroxisome proliferator-activated receptor PPARγ and increased the expression of bone formation proteins BMP2 and RUNX2. Collectively, these results elucidated that YPEP improves osteoporosis by inhibiting lipogenesis to promote bone formation. This study provides novel evidence for the use of YPEP in treating osteoporosis.
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