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Blood to Brain Transfer of Leptin in Normal and Interleukin-1ß-Treated Male Rats¹

Department of Medicine, University of Arizona College of Medicine (S.R., G.C.), Tucson, Arizona 85724-5099; and Amgen, Inc. (M.N.), Thousand Oaks, California 91320-1799

Address all correspondence and requests for reprints to: Dr. Seymour Reichlin, Department of Medicine, University of Arizona College of Medicine, 1501 North Campbell Avenue, P.O. Box 245099, Tucson, Arizona 85724-5099. E-mail: reichlin{at}arizona.edu

To test the hypothesis that leptin was secreted from the brain into the blood of the rat, its concentration was measured in the superior sagittal sinus (SSS; which drains the cerebral cortex) and aortic blood of normal fasting male rats and rats that had been treated with iv or intracerebroventricular (icv) injections of interleukin-1ß (IL-1ß; 100 ng), a cytokine previously shown to induce peripheral leptin secretion. Plasma levels of leptin in SSS were slightly, but significantly, less than those in the aorta in control, saline-injected rats (0.99 ± 0.07 vs. 1.19 ± 0.10 ng/ml; n = 15; P = 0.03) and in rats injected with human IL-1ß iv (1.56 ± 0.12 vs. 1.92 ± 0.15 ng/ml; n = 23; P = 0.004) or icv (1.38 ± 0.11 vs. 1.57 ± 0.12 ng/ml; n = 23; P = 0.008). IL-1ß by either the iv or icv route significantly increased leptin levels in the aorta [1.19 ± 0.10 vs. 1.92 ± 0.15 ng/ml (P = 0.0002) and 1.19 ± 0.10 vs. 1.57 ± 0.12 ng/ml (P = 0.022), respectively]. SSS levels of leptin were also raised after iv or icv injection (P = 0.0002 and P = 0.0053, respectively). These findings demonstrate a net uptake of leptin by the cerebral cortex from peripheral blood in both normal and IL-1ß-treated animals and show that peripheral blood levels of leptin are increased by IL-1ß whether administered icv or iv.

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