HYPOTHALAMIC CART IS A NEW ANORECTIC PEPTIDE REGULATED BY LEPTIN

The mammalian hypothalamus strongly influences ingestive behaviour thr ough several different signalling molecules and receptor systems(1-4). Here we show that CART (cocaine-and amphetamine-regulated transcript) , a brain-located peptide(5-8), is a satiety factor and is closely ass ociated with the actions of two important regulators of food intake, l eptin and neuropeptide Y. Food-deprived animals show a pronounced decr ease in expression of CART messenger RNA in the arcuate nucleus. In an imal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of l eptin to obese mice stimulates CART mRNA expression. When injected int racerebroventricularly into rats, recombinant CART peptide inhibits bo th normal and starvation-induced feeding, and completely blocks the fe eding response induced by neuropeptide Y. An antiserum against CART in creases feeding in normal rats, indicating that CART may be an endogen ous inhibitor of food intake in normal animals.