ARC POMC mRNA and PVN α-MSH are lower in obese relative to lean Zucker rats

Abstract

Effects of obesity on gene expression for opioid peptides and neuropeptide-Y (NPY) in the arcuate nucleus (ARC), and on opioid peptides and α-melanocyte stimulating hormone (α-MSH) in the paraventricular nucleus (PVN) were examined in obese Zucker rats (18 weeks old). Obese Zucker rats are insulin-resistant, diabetic and hyperleptinemic as indicated by high serum glucose, insulin and leptin levels. ARC proOpiomelanocortin (POMC) mRNA levels were significantly lower in the obese relative to lean Zucker rats and ARC proNeuropeptide Y (proNPY) mRNA levels were higher ( P<0.05). There were no differences in proDynorphin and proEnkephalin mRNA levels in the ARC ( P>0.05). Obese Zucker rats had lower α-MSH and dynorphin A 1–17 peptide levels in the paraventricular nucleus (PVN) ( P<0.05), but did not have lower PVN β-endorphin peptide levels ( P>0.05). The decrease in POMC in the ARC and decrease in α-MSH in the PVN seen in the obese Zucker rat in the present study suggest that reduced activity of the melanocortin system in the ARC to PVN pathway may contribute to the related hyperphagia. Reduced activity of the melanocortin system in the ARC to PVN pathway may be due to a disturbance of leptin signaling coupling to POMC.