Previous studies have suggested that
neuropeptide Y (NPY) in the dorsomedial hypothalamus (
DMH) serves as an important signaling
peptide in the regulation of energy balance. To elucidate such actions, we used the adenoassociated virus (AAV) system to alter Npy gene expression in the
DMH and examined the effects of these alterations on food intake and energy balance as well as explored its downstream signaling pathway. We found that AAV-mediated overexpression of NPY in the
DMH of lean rats increased food intake and
body weight, and exacerbated high-fat diet-induced
obesity. Knockdown of NPY expression in the
DMH via AAV-mediated RNA interference ameliorated the
hyperphagia,
obesity, and diabetes of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. NPY knockdown in the
DMH produced a nocturnal and meal size-specific feeding effect. Moreover, we found that knockdown of
DMH NPY expression in intact rats reduced NPY content in the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus and affected within-meal satiation.
DMH NPY knockdown increased the feeding inhibitory and NTS c-Fos responses to peripheral administration of
cholecystokinin. Together, these results indicate that
DMH NPY plays an important role in modulating food intake and energy balance and its dysregulation causes disordered energy balance leading to
obesity.