A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse.

Academic Article

Abstract

  • The central melanocortin system is critical for the long term regulation of energy homeostasis. Null mutations of the melanocortin-4 receptor (MC4-R) are associated with hyperphagia, obesity, and accelerated longitudinal growth in mice and humans. However, little is known about the function of another central melanocortin receptor, the MC3-R. To assess the role of the MC3-R in energy homeostasis, the majority of the mc3r coding sequence was deleted from the mouse genome. In contrast to the MC4-R knockout, which exhibits increased food intake, increased somatic growth, and defects in metabolism, mc3r-/- mice exhibit an exclusively metabolic syndrome. Homozygous null mc3r mice, while not significantly overweight, exhibit an approximately 50% to 60% increase in adipose mass. Mc3r-/- mice also exhibit an unusual increase in respiratory quotient when transferred onto high fat chow, suggesting a reduced ratio of fat/carbohydrate oxidation. Furthermore, male mc3r-/- mice also exhibit an approximately 50% reduction in locomotory behavior on the running wheel, suggesting reduced energy expenditure.
  • Published In

  • Endocrinology  Journal
  • Keywords

  • Absorptiometry, Photon, Adipose Tissue, Animals, Calorimetry, Indirect, Cloning, Molecular, Diet, Energy Metabolism, Gene Targeting, Genetic Vectors, Male, Mice, Mice, Knockout, Obesity, RNA, Messenger, Receptor, Melanocortin, Type 3, Receptors, Corticotropin, Reverse Transcriptase Polymerase Chain Reaction
  • Digital Object Identifier (doi)

    Author List

  • Butler AA; Kesterson RA; Khong K; Cullen MJ; Pelleymounter MA; Dekoning J; Baetscher M; Cone RD
  • Start Page

  • 3518
  • End Page

  • 3521
  • Volume

  • 141
  • Issue

  • 9