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ARC POMC mRNA and PVN alpha-MSH are lower in obese relative to lean zucker rats
1Minnesota Obesity Center and Research Service, VA Medical Center, Minneapolis, MN, USA.
Abstract:
Effects of obesity on gene expression for opioid peptides and neuropeptide-Y (NPY) in the arcuate nucleus (ARC), and on opioid peptides and alpha-melanocyte stimulating hormone (alpha-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 (0.05). Obese Zucker rats had lower alpha-MSH and dynorphin A(1-17) peptide levels in the paraventricular nucleus (PVN) (P<0.05), but did not have lower PVN beta-endorphin peptide levels (0.05). The decrease in POMC in the ARC and decrease in alpha-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.
Insights
Obesity in Zucker rats lowers pro-opiomelanocortin (POMC) and alpha-melanocyte stimulating hormone (alpha-MSH) in key brain areas, suggesting impaired melanocortin system signaling contributes to overeating.
Area of Science:
- Neuroscience
- Endocrinology
- Obesity Research
Background:
- Obesity is linked to hormonal imbalances and altered gene expression in appetite-regulating brain regions.
- The melanocortin system, involving alpha-melanocyte stimulating hormone (alpha-MSH), plays a crucial role in appetite control.
- Zucker rats are a widely used model for studying obesity, insulin resistance, and diabetes.
Purpose of the Study:
- To investigate the effects of obesity on gene expression of opioid peptides and neuropeptide-Y (NPY) in the arcuate nucleus (ARC).
- To examine the impact of obesity on opioid peptides and alpha-melanocyte stimulating hormone (alpha-MSH) levels in the paraventricular nucleus (PVN).
- To explore the relationship between these molecular changes and hyperphagia in obese Zucker rats.
Main Methods:
- Gene expression analysis of opioid peptides and neuropeptide-Y (NPY) mRNA in the ARC of obese and lean Zucker rats.
- Peptide level quantification of alpha-melanocyte stimulating hormone (alpha-MSH) and opioid peptides in the PVN.
- Comparison of molecular markers between 18-week-old obese Zucker rats and their lean counterparts.
Main Results:
- Obese Zucker rats exhibited significantly lower ARC pro-opiomelanocortin (POMC) mRNA levels compared to lean rats.
- ARC proNeuropeptide Y (proNPY) mRNA levels were significantly higher in obese Zucker rats.
- Obese Zucker rats showed decreased alpha-MSH and dynorphin A(1-17) peptide levels in the PVN.
Conclusions:
- Reduced POMC expression in the ARC and diminished alpha-MSH in the PVN suggest impaired melanocortin system activity in obese Zucker rats.
- This impairment in the ARC to PVN pathway may contribute to the hyperphagia observed in obese Zucker rats.
- Disturbances in leptin signaling may underlie the reduced melanocortin system activity in the ARC to PVN pathway.
