Effects of a Jak2 inhibitor on regulation of food intake by leptin and MTII. Sprague Dawley rats (16 wk old, six to eight/group) bearing third cerebroventricular cannula were fasted for 24 h and subsequently pretreated with a cell-permeable Jak2 inhibitor (AG490, 1 nmol) or vehicle 1 h before treatment with leptin (3 μg, icv) or vehicle, and 4 and 24 h food intake was measured. Leptin alone significantly suppressed 24-h food intake (*, P < 0.05); however, pretreatment with the Jak2 inhibitor AG490 completely blocked leptin’s ability to suppress food intake. A separate group of Sprague Dawley rats were fasted for 24 h and pretreated as above with AG490 (1 nmol icv) or vehicle 1 h before treatment with the melanocortin agonist MTII (0.3 nmol icv) or vehicle. MTII significantly reduced 4 and 24-h food intake (P < 0.05), but AG490 pretreatment had no effect on MTII-dependent suppression of food intake.