CART peptide diurnal variations in blood and brain

The central role of CART peptide in feeding, drug abuse and stress has been widely researched however, CART's role in the peripheral system are less explored. CART peptide is present in a variety of peripheral tissues including sympathetic ganglion neurons, adrenal glands, gut, pancreas and blood. Studies that examined circulating CART demonstrated that the active fragment with a molecular weight of CART55-102 is present in the blood of rats and rhesus macaques. Interestingly, CART expression in these species exhibits a distinctive diurnal rhythm which correlates with the respective daily rhythms of corticosterone and feeding. In the rat, adrenalectomy significantly reduces blood CART levels and abolishes its daily rhythm while corticosterone replacement reinstates CART expression to control levels. In addition, direct administration of corticosterone significantly increases CART blood levels while administration of corticosterone synthesis blocker metyrapone, inhibits CART blood levels. These data suggest that the adrenal gland could be a source of blood CART and that glucocorticoids may play a role in the generation of CART's diurnal rhythm. Moreover, fuel availability may be important in the control of CART levels and its daily rhythm, since 24 h food restriction alters CART levels and abolishes its rhythm. In addition to blood, both CART peptide and mRNA exhibit food-dependent diurnal rhythm in discrete rat brain areas including the nucleus accumbens, amygdala and hypothalamus. Altogether, these findings suggest that CART is influenced by hypothalamic-pituitary-adrenal interactions and that it may play a role in multiple physiological processes possibly involving feeding, stress, reward and motivation.