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Feeding effects of hypothalamic injection of melanocortin 4 receptor ligands
S Q Giraudo1, C J Billington, A S Levine
1Department of Medicine, University of Minnesota, Minneapolis, USA.
Abstract:
It has been reported that intraventricular administration of the melanocortin 4 receptor (MC4-R) agonist MT II and antagonist SHU9119 alter food intake. We found that MT II and SHU9119 have extremely potent effects on feeding when injected in the paraventricular nucleus (PVN), a site where MC4-R gene expression is very high. Our finding provides direct evidence that MC4-R signaling is important in mediating food intake and that melanocortin neurons in the PVN exert a tonic inhibition of feeding behavior. Chronic disruption of this inhibitory signal is a possible explanation of the agouti-obesity syndrome.
Insights
Melanocortin 4 receptor (MC4-R) signaling in the paraventricular nucleus (PVN) powerfully influences feeding behavior. Disrupting this MC4-R pathway may contribute to obesity.
Area of Science:
- Neuroscience
- Endocrinology
- Behavioral Science
Background:
- Intraventricular administration of melanocortin 4 receptor (MC4-R) agonists and antagonists has been shown to affect food intake.
- MC4-R gene expression is notably high in the paraventricular nucleus (PVN) of the hypothalamus.
Purpose of the Study:
- To investigate the potent effects of MC4-R agonist MT II and antagonist SHU9119 on feeding behavior when injected directly into the PVN.
- To provide direct evidence for the role of MC4-R signaling in the PVN in regulating food intake.
Main Methods:
- Direct injection of MT II and SHU9119 into the paraventricular nucleus (PVN) in a rodent model.
- Observation and quantification of feeding behavior following PVN injections.
Main Results:
- Both MT II and SHU9119 demonstrated extremely potent effects on feeding when administered specifically within the PVN.
- These findings indicate that MC4-R signaling within the PVN is critical for modulating food intake.
Conclusions:
- Melanocortin neurons in the PVN exert a tonic inhibitory control over feeding behavior.
- Chronic disruption of this inhibitory MC4-R signaling pathway in the PVN is a potential mechanism underlying the agouti-obesity syndrome.