Blood to brain transfer of leptin in normal and interleukin-1beta-treated male rats

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-1beta (IL-1beta; 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-1beta 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-1beta 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-1beta-treated animals and show that peripheral blood levels of leptin are increased by IL-1beta whether administered icv or iv.