Ma. Asnicar et al., Absence of cocaine- and amphetamine-regulated transcript results in obesity in mice fed a high caloric diet, ENDOCRINOL, 142(10), 2001, pp. 4394-4400
Cart (cocaine- and amphetamine-regulated transcript) was first identified t
o be a major brain mRNA up-regulated by cocaine and amphetamine. The CART p
rotein 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, sho
wed statistically significant increases in weekly food consumption, body we
ight, 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 mi
ce showed no weight variations attributable to caloric contents of the diet
at that age. Contrary to the obese phenotypes shown in MC4R-, proopiomelan
ocortin-, 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 proop
iomelanocortin or leptin in the regulation of energy homeostasis.