with a 14-day pump (Model 2002, Durect) dispensing leptin at a rate 450 ng/h above baseline. This means that for wild-type animals, pumps delivering PBS were replaced with pumps delivering leptin at 450 ng/h, and for ob/ob animals, pumps delivering leptin at 150 ng/h were replaced with pumps delivering leptin at 600 ng/h. Body weight was recorded daily and food intake every 6 days. After 12 days pumps were removed and replaced with pumps dispensing leptin at baseline (PBS for wild- type animals and 150 ng/h for ob/ob animals). Immunohistochemistry Mice were injected with either leptin (2 mg/kg, intraperitoneal) or vehicle (PBS). 30 min after injection animals were anesthetized with isoflurane and perfused with 10% neutral buffered formalin (Sigma, St. Louis, MO). Brains were removed by dissection and soaked in formalin overnight at 4uC. 50 mm sections were prepared and stained for pSTAT3 as follows[10]. 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