Assessment of a small molecule melanocortin-4 receptor-specific agonist on energy homeostasis

David Cepoi, Teresa Phillips, Mary Cismowski, Val S. Goodfellow, Nick Ling, Roger D. Cone, Wei Fan

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The central melanocortin system has been demonstrated to play an important role in regulating different aspects of energy homeostasis. Understanding the specific contributions of MC3 and MC4 receptors, however, requires specific agonists and antagonists for each of the predominant forms of brain melanocortin receptors, MC3-R and MC4-R. We report here the characterization of a small peptide mimetic MC4-R-specific agonist that possesses both high affinity (Ki=11.3 nM) and potency (EC50=1.62 nM) in vitro and is capable of inhibiting feeding behavior in mice when administered intracerebroventricularly (icv). Depending on the paradigm, acute (1 h following an overnight fast) or long-term (greater than 6 h under normal nocturnal feeding conditions) feeding inhibition was observed following icv injection. No effect on long-term feeding inhibition was observed with this compound in MC4-R knockout mice, and central administration of this compound had no effect on either metabolic rate or insulin release.

Original languageEnglish (US)
Pages (from-to)64-71
Number of pages8
JournalBrain research
Volume1000
Issue number1-2
DOIs
StatePublished - Mar 12 2004

Keywords

  • Feeding
  • Ingestive behaviors
  • Melanocortin receptor
  • Neural basis of behavior
  • Obesity
  • POMC
  • Small molecule agonist

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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