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 NPY model.

METHODS

To study the role of mesenchymal-derived NPY, we crossed conditional NPY (NPY) mice with Prx1cre to generate PrxNPY mice. The bone phenotype was assessed using micro-CT. The skeletal phenotype of PrxNPY mice was subsequently compared to global NPY 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 PrxNPY mice with no changes to cancellous bone. This was the opposite phenotype to global NPY mice generated from the same conditional allele. Male NPYmice have increased adiposity, while PrxNPY 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.