Involvement of the histaminergic system in leptin-induced suppression of food intake

The ob gene product leptin is secreted from white adipose tissue, and may r egulate food intake by acting on the hypothalamus in the central nervous sy stem, But the mechanism of this effect is still unclear. The central histam inergic system has been suggested to participate in the control of various physiological functions, particularly in feeding behavior, as it mediates a norectic signals like leptin. Thus, we hypothesized that the central histam inergic system is a target for leptin in its control of feeding. To prove t his, we first examined the effect of i.p. administration of alpha-fluoromet hylkistidine (FMH), a specific and irreversible inhibitor of histidine deca rboxylase, on leptin-induced suppression of food intake in normal C57BL str ain mice. Leptin treatment (1.3 mg/kg, i.p.) significantly reduced food int ake by 60% of that of control at 6 h and by 54% at 24 h compared with contr ol. When mice were injected with FMH (100 mg/kg, i.p.) before being given l eptin, leptin-induced suppression of food intake was abolished and there wa s no significant difference compared with that of control. Additionally, we further examined the effects of leptin on food intake in mutant mice lacki ng histamine H-1 receptors (H1R-KO mice). Leptin injection significantly re duced food intake by 56% of that of control at 6 h and by 79% at 24 h in wi ld-type mice (WT mice), but not in H1R-KO mice. This finding suggests that leptin affects the feeding behavior through activation of the central hista minergic system via histamine H-1 receptors. (C) 1999 Elsevier Science Inc.