Neuropeptide Y (NPY), an orexigenic hypothalamic neuropeptide, causes hyperphagia and obesity in the adult. Our previous studies revealed that maternal diabetes suppressed, while uteroplacental insufficiency causing intrauterine growth retardation, enhanced fetal and postnatal brain NPY synthesis (Endocrinol 1997). To determine the short and long term biological effects of altered postnatal brain NPY levels, we instilled 1 μg of NPY in 2.5 μl vehicle (NPY; n=12) or 2.5 μl of vehicle (CON; n=12) intracerebroventricularly (ICV) in newborn rats daily from 2 to 7 days of age. Body weight (B.W.) was assessed daily between 2d to 61d, and food intake was quantitated weekly from 22d (postweaning) to 61d. NPY caused a ≈25% increase in B.W. gain on day 3 when compared to CON (NPY=1.58±0.07g vs. CON=1.20±0.06g; p < 0.05). This difference was no longer apparent between 8d to 22d. Sex specific differences in B.W. gain were observed in the 36 to 61d animals (61d male -358±11g vs. female - 240±11g; p< 0.05). A decline in the 61d female B.W. gain (221±10g) was noted in the NPY group versus the age-matched CON (242±10), with no change in the male. Concomitantly, a decline in total food intake was noted in the NPY-36 to 61d male (11%; p < 0.05) and female (20%; p < 0.05) progeny when compared to the age matched CON. We conclude that neonatal ICV NPY instillation 1] has a short term positive effect upon neonatal body weight gain, and 2] exerts a long term imprinted negative effect upon adult food intake and female body weight gain. We speculate that persistent changes in endogenous NPY synthesis and/or a downregulation of the NPY-Y5 receptors may mediate these long term effects of diminished NPY sensitivity.

Supported by NIH-HD25024