CART in feeding and obesity

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CART (cocaine- and amphetamine-regulated transcript) peptides are neurotransmitters that have received much attention as mediators of feeding behavior and body-weight regulation in mammals. CART peptides and their mRNAs are found in many brain regions and in peripheral tissues that are involved in feeding, and many animal studies implicate CART as an inhibitor of feeding. Animal studies also demonstrate that CART expression is regulated by both leptin and glucocorticoids, two hormones known to be associated with the regulation of body weight. A recent study also links a mutation in the CART gene to obesity in humans. These peptides might become targets for drug development in the area of obesity.

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Anatomical studies

Koylu et al. [11] suggested that CART might be involved in feeding after noting that CART immunoreactivity was localized to brain regions associated with feeding behavior 11, 12, notably the ventromedial nucleus (VMN), dorsomedial nucleus (DMN), lateral hypothalamus (LH), arcuate nucleus (Arc), paraventricular nucleus of the hypothalamus (PVN) and nucleus accumbens, which is a neural substrate for the expression of reward for behaviors such as food intake [13]. It has since been demonstrated

Functional studies

Given the anatomical findings, interest quickly turned to testing the effects on feeding behavior of intracerebroventricular (ICV) CART peptides and antibodies to them. Two groups 27, 29, 33 showed that feeding in rats was increased by ICV administration of antibodies against CART peptides, and Kristensen et al. [29] showed that CART peptides antagonized feeding, including feeding induced by the infusion of NPY, which is one of the most significant central stimulators of feeding [34].

CART and obesity

Several genetic findings link CART to human obesity. The human CART gene is a positional candidate for obesity because it maps to human chromosome 5q13–14 62, 63, which has been shown to be a susceptibility locus for obesity [64]. Animal models also support a role for CART in obesity. As mentioned above, mice that have a targeted deletion of the CART gene become more obese when fed a high-fat diet from weaning than wild-type littermates [55]. Interestingly, CART-deficient animals did not show

Conclusions

A confluence of findings shows that CART has a substantial role in the regulation of feeding and body weight. In spite of some of the ambiguities in the animal studies, the bulk of the data show that CART is a potent modulator of feeding in mammals. The studies of human genetic mutations, which show a substantial impact on body weight, are of great interest. CART represents a definite target for the treatment of obesity in these genetically determined cases and might represent a useful drug

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