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

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 alpha-fluoromethylhistidine (alpha-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 microg at 09:00 h) in fasted rats caused a decrease in food intake. In contrast, central administration of alpha-FMH (11, 22 and 112 microg at 09:00 h) increased food intake. Prior administration of alpha-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, alpha-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.