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 (Ki) 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.
Banks
W A
WA
Veterans Affairs Medical Center, New Orleans, LA 70146, USA.
Kastin
A J
AJ
Huang
W
W
Jaspan
J B
JB
Maness
L M
LM
D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007328:Insulin / Q000378:metabolism*; D020738:Leptin; D051379:Mice; D009765:Obesity / Q000378:metabolism; D011506:Proteins / Q000493:pharmacokinetics*; D011859:Radiography; D011994:Recombinant Proteins / Q000493:pharmacokinetics
D007328:Insulin; D020738:Leptin; D011506:Proteins; D011994:Recombinant Proteins