The role of hypothalamic histamine in leptin-induced suppression of short-term food intake in fasted rats

Abstract

Objective: Leptin suppresses food intake; however, the precise mechanism is not fully understood. Histamine (HA), which acts as a neurotransmitter in the central nervous system, has also been shown to be involved in feeding and exerts an inhibitory effect through activation of H 1 receptors. Therefore, we studied the possible role of HA in short-term leptin-induced suppression of food intake. Methods: We studied the 6-h feeding response of overnight-fasted adult (200 g) male Wistar rats to leptin and the HA synthesis inhibitor α-fluoromethylhistidine (α-FMH). Levels of transcription for neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH), as well as hypothalamic content of HA and the HA metabolite telemethyl-HA were investigated. Results: Central administration of leptin (3, 5 and 10 μg at 09:00 h) in fasted rats caused a decrease in food intake. In contrast, central administration of α-FMH (11, 22 and 112 μg at 09:00 h) increased food intake. Prior administration of α-FMH prevented the leptin-induced decrease in food intake. Leptin decreased hypothalamic histamine content, while increasing the ratio between telemethyl-HA and HA, indicating that leptin reduces HA metabolism. Finally, α-FMH suppressed basal and leptin-induced CRH expression while stimulating NPY expression in fasted rats. Conclusion: Histamine is involved in leptin-induced inhibition of food intake. The role of histamine may be mediating, i.e. leptin may directly activate and/or change the metabolism of the histaminergic system. Alternatively, the histaminergic system may be involved in a permissive manner.