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Leptin increases serotonin turnover by inhibition of brain nitric oxide synthesis
Gioacchino Calapai, Francesco Corica, Andrea Corsonello, Lidia Sautebin, Massimo Di Rosa, Giuseppe M. Campo, Michele Buemi, Vittorio Nicita Mauro, Achille P. Caputi
Gioacchino Calapai, Francesco Corica, Andrea Corsonello, Lidia Sautebin, Massimo Di Rosa, Giuseppe M. Campo, Michele Buemi, Vittorio Nicita Mauro, Achille P. Caputi
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Leptin increases serotonin turnover by inhibition of brain nitric oxide synthesis

Abstract

Leptin administration inhibits diencephalic nitric oxide synthase (NOS) activity and increases brain serotonin (5-HT) metabolism in mice. We evaluated food intake, body-weight gain, diencephalic NOS activity, and diencephalic content of tryptophan (TRP), 5-HT, hydroxyindoleacetic acid (5-HIAA), and 5-HIAA/5-HT ratio after intracerebroventricular (ICV) or intraperitoneal (IP) leptin injection in mice. Five consecutive days of ICV or IP leptin injections induced a significant reduction in neuronal NOS (nNOS) activity, and caused a dose-dependent increase of 5-HT, 5-HIAA, and the 5-HIAA/5-HT ratio. Diencephalic 5-HT metabolism showed a significant increase in 5-HT, 5-HIAA, and the 5-HIAA/5-HT ratio 3 hours after a single leptin injection. This effect was maintained for 3 hours and had disappeared by 12 hours after injection. After a single IP leptin injection, the peak for 5-HT, 5-HIAA, and the 5-HIAA/5-HT ratio was achieved at 6 hours. Single injections of ICV or IP leptin significantly increased diencephalic 5-HT content. Leptin-induced 5-HT increase was antagonized by the coadministration of L-arginine only when the latter was ICV injected, whereas D-arginine did not influence leptin effects on brain 5-HT content. Finally, in nNOS-knockout mice, the appetite-suppressant activity of leptin was strongly reduced, and the leptin-induced increase in brain 5-HT metabolism was completely abolished. Our results indicate that the L-arginine/NO pathway is involved in mediating leptin effects on feeding behavior, and demonstrate that nNOS activity is required for the effects of leptin on brain 5-HT turnover.

Authors

Gioacchino Calapai, Francesco Corica, Andrea Corsonello, Lidia Sautebin, Massimo Di Rosa, Giuseppe M. Campo, Michele Buemi, Vittorio Nicita Mauro, Achille P. Caputi

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