Leptin enters the brain by a saturable system independent of insulin

Leptin, or OB protein, is produced by fat cells and may regulate body weight by acting on the brain. To reach the brain, circulating leptin must cross the blood-brain barrier (BBB). Intravenously injected radioiodinated leptin ( 125I-leptin) had an influx constant (K i) into brain of (5.87)10 −4 ml/...

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Bibliographic Details
Published in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 1996, Vol.17 (2), p.305-311
Main Authors: Banks, William A., Kastin, Abba J., Huang, Weitao, Jaspan, Jonathan B., Maness, Lawrence M.
Format: Article
Language:English
Subjects:
Animals
Arcuate nucleus
Autoradiography
Blood-brain barrier
Blood-Brain Barrier - drug effects
Brain - cytology
Brain - diagnostic imaging
Brain - metabolism
Choroid plexus
Distribution
Hypothalamus
Injections, Intraperitoneal
Injections, Intravenous
Injections, Intraventricular
Insulin
Insulin - metabolism
Leptin
Mice
OB protein
Obesity
Obesity - metabolism
Proteins - pharmacokinetics
Radiography
Recombinant Proteins - pharmacokinetics
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Summary:Leptin, or OB protein, is produced by fat cells and may regulate body weight by acting on the brain. To reach the brain, circulating leptin must cross the blood-brain barrier (BBB). Intravenously injected radioiodinated leptin ( 125I-leptin) had an influx constant (K i) into brain of (5.87)10 −4 ml/g-min, a rate 20 times greater than that of labeled albumin. Unlabeled leptin inhibited the influx of 125I-leptin in a dose-dependent manner whereas unlabeled tyrosine and insulin, which have saturable transport systems, were without effect. HPLC and acid precipitation showed that the radioactivity in brain and serum represented intact 125I-leptin. About 75% of the extravascular 125I-leptin in brain completely crossed the BBB to reach brain parenchyma. Autoradiography detected uptake at the choroid plexus, arcuate nuclei of the hypothalamus, and the median eminence. Saturable transport did not occur out of the brain. The results show that leptin is transported intact from blood to brain by a saturable system.
ISSN:0196-9781
1873-5169
DOI:10.1016/0196-9781(96)00025-3