Article

Transgenic Research

, Volume 9, Issue 2, pp 145-154

First online:

Role of the melanocortin-4 receptor in metabolic rate and food intake in mice

  • Airu S. ChenAffiliated withDepartment of Metabolic Disorders, Merck Research Laboratories
  • , Joseph M. MetzgerAffiliated withDepartment of Animal Pharmacology, Merck Research Laboratories
  • , Myrna E. TrumbauerAffiliated withDepartment of Metabolic Disorders, Merck Research Laboratories
  • , Xiao-ming GuanAffiliated withDepartment of Metabolic Disorders, Merck Research Laboratories
  • , Hong YuAffiliated withDepartment of Metabolic Disorders, Merck Research Laboratories
  • , Easter G. FrazierAffiliated withDepartment of Metabolic Disorders, Merck Research Laboratories
  • , Donald J. MarshAffiliated withDepartment of Metabolic Disorders, Merck Research Laboratories
  • , Michael J. ForrestAffiliated withDepartment of Animal Pharmacology, Merck Research Laboratories
  • , Shobhna Gopal-TruterAffiliated withDepartment of Comparative Medicine, Merck Research Laboratories
    • , Jill FisherAffiliated withDepartment of Comparative Medicine, Merck Research Laboratories
    • , Ramon E. CamachoAffiliated withDepartment of Animal Pharmacology, Merck Research Laboratories
    • , Alison M. StrackAffiliated withDepartment of Animal Pharmacology, Merck Research Laboratories
    • , Theodore N. MellinAffiliated withDepartment of Animal Pharmacology, Merck Research Laboratories
    • , D. Euan MacIntyreAffiliated withDepartment of Animal Pharmacology, Merck Research Laboratories
    • , Howard Y. ChenAffiliated withDepartment of Animal Pharmacology, Merck Research Laboratories
    • , Lex H.T. Van der PloegAffiliated withDepartment of Metabolic Disorders, Merck Research Laboratories

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Abstract

We evaluated the role of the melanocortin-4 receptor (MC-4R) in the control of metabolic rate and food intake in mice. Intraperitoneal administration of the non-selective MC-R agonist melanotan II (MT-II; a cyclic heptapeptide) increases metabolic rate in wildtype mice, while MC-4R knockout mice are insensitive to the effects of MT-II on metabolic rate. MC-4R knockout mice are also insensitive to the effects of MT-II on reducing food intake. We conclude that MC-4R can mediate control of both metabolic rate and food intake in mice. We infer that a role for MC-3R in mediating the acute effects of MT-II on basal metabolic rate and food intake in wildtype mice seems limited.

food intake melanocortin-4 receptor metabolic rate MT-II