Absence of cocaine- and amphetamine-regulated transcript results in obesity in mice fed a high caloric diet.
Cart (cocaine- and amphetamine-regulated transcript) was first identified to be a major brain mRNA up-regulated by cocaine and amphetamine. The CART protein has been established as a satiety factor closely associated with the action of leptin. To assess CART's role as an anorexigenic signal, we have generated CART-deficient mice by gene targeting. On a high fat diet, CART-deficient and female heterozygous mice, but not male heterozygous mice, showed statistically significant increases in weekly food consumption, body weight, and fat mass compared with their wild-type littermates. Furthermore, CART-deficient and female heterozygous mice were significantly heavier when fed a high fat diet than on a regular chow diet at 17 wk of age and at the 14th wk of the feeding studies. However, wild-type or male heterozygous mice showed no weight variations attributable to caloric contents of the diet at that age. Contrary to the obese phenotypes shown in MC4R-, proopiomelanocortin-, or leptin-deficient mice, our results showed that CART deficiency predisposed mice to become obese on a calorically dense diet. The results also show that CART may not be a major anorectic signal compared with proopiomelanocortin or leptin in the regulation of energy homeostasis.
Asnicar
M A
MA
Division of Endocrine Research, Eli Lilly & Co., Indianapolis, Indiana 46285, USA.
Smith
D P
DP
Yang
D D
DD
Heiman
M L
ML
Fox
N
N
Chen
Y F
YF
Hsiung
H M
HM
Köster
A
A
D000818:Animals; D004032:Diet; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics*; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein