NPY deficiency protects against osteoporosis by altering bone lipid metabolism

Osteoporosis is a major global health issue characterized by imbalanced bone remodeling. Neuropeptide Y (NPY) is a key regulator of energy metabolism and bone homeostasis, but its role in osteoporosis progression remains poorly defined.

This study enrolled 74 participants, including 38 osteoporosis patients and 36 controls, and evaluated the relationship of NPY levels with other clinical indicators. NPY knockout and wild-type mice with or without ovariectomy were used to investigate the role of NPY in bone loss and changes in the bone lipid profile. Bone loss was assessed by micro-computed tomography. Tissue lipidomic analysis was performed by liquid chromatography mass spectrometry.

The serum NPY levels of female patients with osteoporosis were significantly elevated compared with the corresponding control group. In female patients, lumbar spine T-score, spin T-score and vitamin D level showed significant negative correlation with NPY level. NPY knockdown protected against ovariectomy-induced bone loss, and their lipids in bone were profiled. As many as 18 lipids classes were quantified, and overall levels of phosphatidylinositol and lysophosphatidyl choline were greatly changed with NPY silence. In detail, 49 lipids were significantly altered due to NPY in OVX mice, 12 of which were related to osteoporosis. Interestingly, TAG was the main component among them, and it indicated some specific TAG could be connected with NPY on osteoporosis.

NPY ablation protects against osteoporosis by altering bone lipid metabolism. Therefore, NPY could be a potential target for osteoporosis treatment.