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
  • 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