Neuropeptide Y (NPY) has been shown to have a prominent role in the control of bone formation through the regulation of osteoblast activity. We aimed to investigate the role of hypothalamus-derived NPY in bone metabolism.
Accordingly, adeno-associated virus (AAV)-mediated RNA interference (RNAi) was utilized to downregulate NPY gene expression in rats fed regular chow (RC) or a high-fat diet (HF). The serum concentrations of glucose, insulin, corticosterone, osteocalcin, insulin-like growth factor (IGF-1), triglycerides (TC), and cholesterol (TG) and fat mass and bone mineral density (BMD) were measured to assess the effect of NPY knockdown on basal and obesity-induced BMD. Forkhead transcription factor (FoxO1) and activating transcription factor 4 (ATF4) were measured to explore the molecular mechanism of the effect of dorsomedial nucleus (DMH) NPY knockdown on bone formation.
Our results showed that DMH NPY knockdown enhanced basal and the obesity-induced decrease in BMD and osteocalcin and promoted the phosphorylation of FoxO1 and reduced the expression of ATF4.
Our data suggest that DMH NPY knockdown can alter bone metabolism.