Leptin is mainly synthesized and secreted by fat cells in proportion to adipose tissue mass. Under physiological conditions, this hormone reduces food intake and increases thermogenesis through interactions with neurons in the central nervous system (CNS). However transport of leptin into the CNS via the blood brain barrier (BBB) is saturable and in obesity the feedback signal to the brain is markedly insufficient.

In recent experiments we have shown, that intranasal (i.n.) delivery of leptin reduces food intake in rats. The aim of the present study was to explore the distribution of i.n. delivered leptin within brain, blood and peripheral tissues. Application of ¹²⁵I-leptin (0.03 mg/kg, 0.1 mg/kg, 0.2 mg/kg) into male Wistar rats' nares (n = 8 per group) leads to supraphysiological brain leptin concentrations 30 min after application, with contents in the hypothalamus (7.3 ± 2.6 ng/g, 5.9 ± 1.6 ng/g, 13.8 ± 5.7 ng/g; P = 0.023, F=6.157) being significantly higher than the brain average (1.2 ± 0.2 ng/g, 3.9 ± 1.0 ng/g, 6.0 ± 1.9 ng/g). In contrast, contents in the occipital/entorhinal cortex were lower than the brain average, indicating a minor participation of the transport via cerebrospinal fluid (CSF), which would have favored CSF-exposed surfaces.

In experiments employing the application of unlabeled leptin intravenously (i.v.), we were able to show that excess blood leptin does not diminish brain uptake of i.n. leptin (as indicated by ¹²⁵I-leptin), supporting a direct transport from nose to brain by circumvention of the BBB.

This study thus clearly demonstrates a rapid and highly effective transport of leptin from nose to brain.