Horm Metab Res 1996; 28(12): 653-658
DOI: 10.1055/s-2007-979872
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© Georg Thieme Verlag Stuttgart · New York

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

M. Van Heek1 , D. E. Mullins1 , M. A. Wirth2 , M. P. Graziano1 , A. B. Fawzi1 , D. S. Compton1 , C. F. France1 , L. M. Hoos1 , R. L. Casale2 , E. J. Sybertz1 , C. D. Strader1 , H. R. Davis1  Jr. 
  • 1Department of CNS and Cardiovascular Pharmacology
  • 2Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, New Jersey, U.S.A.
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23. April 2007 (online)


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.