THE RELATIONSHIP OF TISSUE LOCALIZATION, DISTRIBUTION AND TURNOVER TOFEEDING AFTER INTRAPERITONEAL I-125 LEPTIN ADMINISTRATION TO OB OB AND DB/DB MICE/

Brain and whole body localization and distribution of I-125-leptin was determined after intraperitoneal administration to ob/ob and db/db mi ce, and was compared to inhibition of food intake. Food intake was not significantly inhibited at 3 hours postinjection, but was decreased s ignificantly at 6 h (p < 0.0007) and 24 h (p < 0.02) in ob/ob mice, ti mes at which > 97% of the radioactive dose was found in the urine. The highest concentrations of I-125-leptin at all time-points were found in the serum, liver and kidneys. These findings were verified by whole body autoradiography. Virtually no I-125-leptin was found in the CNS at later time-points in either ob/ob or db/db mice. Coronal sectioning of entire brains from ob/ob and db/db mice revealed I-125 radioactivi ty localized to the choroid plexus and in the ventricular space, but n ot in other CNS regions. No differences in localization, accumulation, or clearance of I-125-leptin in ob/ob vs. db/db mice were found in an y of the tissues studied. The present studies demonstrate that the inh ibitory effect of leptin on food intake in the ob/ob mouse persists fo r up to 24 hours after a single dose, despite the complete degradation and elimination of the labeled leptin during the first several hours after injection.