Divergent effects of peripheral and global neuropeptide Y deletion.

OBJECTIVES Neuropeptide Y (NPY) is involved in the coordination of bone mass and adiposity. However, multiple NPY sources exist and their individual contribution to the skeleton and adiposity not known. The objectives of our study were to evaluate the effects of peripheral mesenchymal derived NPY to the skeleton and adiposity and to compare them to the global NPYKO model. METHODS To study the role of mesenchymal-derived NPY, we crossed conditional NPY (NPYfl/fl) mice with Prx1cre to generate PrxNPYKO mice. The bone phenotype was assessed using micro-CT. The skeletal phenotype of PrxNPYKO mice was subsequently compared to global NPYKO model. We evaluated body weight, adiposity and functionally assessed the feeding response of NPY neurons to determine whether central NPY signaling was altered by Prx1cre. RESULTS We identified the increase in cortical parameters in PrxNPYKO mice with no changes to cancellous bone. This was the opposite phenotype to global NPYKO mice generated from the same conditional allele. Male NPYKOmice have increased adiposity, while PrxNPYKO mice showed no difference, demonstrating that local mesenchymal-derived NPY does not influence adiposity. CONCLUSION NPY mediates both positive and negative effects on bone mass via separate regulatory pathways. Deletion of mesenchymal-derived NPY had a positive effect on bone mass.