The relationship of tissue localization, distribution and turnover to feeding after intraperitoneal 125I-leptin administration to ob/ob and db/db mice.
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 at3 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 timepoints 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.
Van Heek
M
M
Department of CNS and Cardiovascular Pharmacology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Mullins
D E
DE
Wirth
M A
MA
Graziano
M P
MP
Fawzi
A B
AB
Compton
D S
DS
France
C F
CF
Hoos
L M
LM
Casale
R L
RL
Sybertz
E J
EJ
Strader
C D
CD
Davis
H R
HR
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002552:Cerebral Ventricles / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000378:metabolism; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D020738:Leptin; D008099:Liver / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D020738:Leptin; D011506:Proteins