A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse.
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.
Butler
A A
AA
Vollum Institute, Oregon Health Sciences University, Portland 97201-3098, USA.
Kesterson
R A
RA
Khong
K
K
Cullen
M J
MJ
Pelleymounter
M A
MA
Dekoning
J
J
Baetscher
M
M
Cone
R D
RD
D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002153:Calorimetry, Indirect; D003001:Cloning, Molecular; D004032:Diet; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D018390:Gene Targeting; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044104:Receptor, Melanocortin, Type 3; D018043:Receptors, Corticotropin / Q000172:deficiency* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D044104:Receptor, Melanocortin, Type 3; D018043:Receptors, Corticotropin