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Ginkgo biloba extract (GbE) stimulates the hypothalamic serotonergic system and attenuates obesity of ovariectomized rats


Menopause is associated with increased risk to develop obesity but the mechanisms involved are not fully understood. We have shown that Ginkgo biloba (GbE) improved diet-induced obesity. Since GbE might be effective in the treatment of obesity related to menopause, without bringing the side effects of hormone replacement therapy, we investigated the effect of GbE on hypothalamic systems controlling energy homeostasis. Wistar rats were either ovariectomized (OVX) or sham-operated. After 2 months, either of GbE or vehicle were administered daily by gavage for 14 days. A subset of these animals received an intracerebroventricular (i.c.v.) injection of 300µg of serotonin or vehicle and the food intake was measured after 12 and 24 hours. Another subset was submitted to the in vivo microdialysis experiment, where 5-HT extracellular levels of medial hypothalamus were measured by HPLC with electrochemical detection, either before and up to 2 hours after the administration of of GbE. Additional animals were used for quantification of 5-HT1A, 5-HT1B, 5-HT2C, 5-HTT and POMC hypothalamic protein levels by Western blotting. OVX increased food intake and body weight and GbE reduced food intake of OVX rats. I.c.v. serotonin significantly reduced food intake in Sham, Sham+GbE and OVX+GbE groups while it failed to do so in the OVX group. In the ovariectomized rats, GbE stimulated 5-HT microdialysate levels while it reduced hypothalamic 5-HTT protein levels. The results indicate that GbE improves the ovariectomy-induced resistance to serotonin hypophagia, at least in part through stimulation of the hypothalamic serotonergic activity. Since body weight gain is one of the most important consequences of menopause, the stimulation of the serotonergic transmission by GbE might represent a potential alternative therapy for menopause-related obesity. (AU)

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