Separate systems for serotonin and leptin in appetite control

Appetite control involves an integration of the drive signals arising form energy stores in the body with the satiety signals generated by periodic ep isodes of food consumption. Serotonin (5-hydroxytryptamine, 5-HT) has been implicated in the processes of within-meal satiation and postmeal satiety ( 5-HT1B and 5-HT2C postsynaptic receptors) which are concerned with the sign als arising form the pattern of food intake. Central nervous system (CNS) 5 -HT is sensitive to circulating levels of the precursor tryprophan, certain macronutrients and peripheral satiety factors such as cholecystokinin (CCK ) and enterostatin. Hypothalamic 5-HT receptor systems inhibit neuropeptide Y (NPY), a potent stimulator of hunger and food intake. in contrast to the linking of 5-HT with the consequences of food ingestion, the hormone lepti n (OB protein) is regarded as a signal linking adipose tissue status with a number of key CNS circuits. Leptin itself stimulates CNS leptin receptors (OB-r receptor) which link with pro-opiomelanocortin (POMC)/MC-4 receptors. The effects of leptin may also be modulated by factors such as the cortico trophin-releasing factor (CRF), cocaine and amphetamine-regulated transcrip t (CART), orexins and galanin. Very little evidence exists to support any d irect link between the actions of 5-HT and leptin, suggesting that they are separate systems. 5-HT is a part of an integrated network for short-acting satiety signals (episodic in nature), and leptin is a hormonal indicator o f long-term (tonic) energy reserves. At a conceptual level, these may repre sent the distinction between 'satiety' and 'drive'. Interestingly, both 5-H T and leptin modulate the action of NPY, which may form a part of a common output pathway for the expression of appetite.