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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.

Brain Research
|December 16, 1998
PubMed

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.

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