The aim of the present study was to obtain evidence for the possible modulatory effect of leptin on glucosensing capacity in hypothalamus and hindbrain of rainbow trout. In a first experiment, trout were injected ICV with saline alone or containing increased doses of leptin (0.3-30 microg microl(-1)). Leptin induced in general in both hypothalamus and hindbrain dose-dependent changes in parameters related to glucosensing (increased glycogenic and glycolytic potentials together with increased GK activity, and increased mRNA levels of genes involved in glucosensing response) compatible with those occurring under hyperglycemic conditions, a situation that is known to produce anorexia. The anorectic action of leptin in our experimental conditions was observed in a second experiment. The specificity of leptin action was tested in a third experiment in which trout were injected ICV with saline, or leptin alone, or leptin plus agents known to inhibit leptin signaling pathways in mammals. The results obtained suggest that the central action of leptin on glucosensing system can be related to the JAK/STAT and IRS-PI(3)K pathways. Finally, we also provide evidence for a peripheral effect of central leptin treatment (increased liver glycogenolytic potential), which could be associated with increased sympathetic activity.