The Relationship of Tissue Localization, Distribution and Turnover to Feeding After Intraperitoneal ¹²⁵I-Leptin Administration to ob/ob and db/db Mice

Abstract

Brain and whole body localization and distribution of ¹²⁵I-leptin was determined after intraperitoneal administration to ob/ob and db/db mice, and was compared to inhibition of food intake. Food intake was not significantly inhibited at 3 hours post-injection, but was decreased significantly at 6 h (p < 0.0007) and 24 h (p < 0.02) in ob/ob mice, times at which > 97% of the radioactive dose was found in the urine. The highest concentrations of ¹²⁵I-leptin at all time-points were found in the serum, liver and kidneys. These findings were verified by whole body autoradiography. Virtually no ¹²⁵I-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 ¹²⁵I radioactivity localized to the choroid plexus and in the ventricular space, but not in other CNS regions. No differences in localization, accumulation, or clearance of ¹²⁵I-leptin in ob/ob vs. db/db mice were found in any of the tissues studied. The present studies demonstrate that the inhibitory effect of leptin on food intake in the ob/ob mouse persists for 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.

Key words

Leptin - Feeding - Tissue Distribution - ob/ob, db/db