Analysis of leptin-induced anorexia : Involvement of serotonin and nitric oxide

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Leptin is an adipocytokine, released from adipose tissue. Leptin is a strong anorectic factor by acting the hypothalamus which control food intake. It is well known that mice deficient of leptin display a marked hyperphagia and obesity. However, mechanism of leptin-induced hypophagia is not yet clarified. In this research, the involvement of serotonin(5-HT) and nitric oxide(NO) in anorexia elicited by leptin in mice. The 5-HT depleter significantly suppressed leptin-induced hypophagia. The 5-HT2B/2C receptor antagonist also reduced anorexia induced by leptin. Therefore, the 5-HT2B/2C receptor activation is involved in leptin-induced hypophagia. We found that leptin did not change brain NOx levels in staraved mice, although leptin inhibited food intake. The serum leptin levels were elevated by pretreatment with the 5-HT precursor, 5-hydroxytryptophan(5-HTP). Hyperleptinemia by 5-HTP is antagonized by streptozotocin which deplets insulin. Furthermore, increases in serum leptin levels induced by 5-HTP are inhibited by the NO synthesis inhibitor. These results suggest that leptin secretion may be controlled by 5-HT and NO and that 5-HT and NO play a significant role in leptin-induced anorexia.