A Single Dose of Ginkgo biloba Extract Induces Gene Expression of Hypothalamic Anorexigenic Effectors in Male Rats

Abstract

Previous studies have shown that Ginkgo biloba extract (GbE) reduces food intake and body mass gain and regulates proteins related to lipid metabolism in obese rats. In ovariectomized rats, GbE restored the hippocampal and hypothalamic serotonergic system activity, favoring the spontaneous feeding decrement. Considering the promising hypophagic effect of GbE, this study aimed to investigate the effect of a single acute dose on hypothalamic pathways that regulate feeding behavior in male rats. Four-month-old Wistar male rats received either a single acute oral GbE dose (500 mg/kg) or vehicle. Food intake and body mass were measured after 1, 4, 12, and 24 h. Rats were euthanized, and hypothalami were removed for mRNA quantification of anorexigenic (POMC/CART) and orexigenic (AgRP/NPY) neuropeptides, leptin/serotonin receptors (5HT1A, 5HT1B, 5HT2C), and serotonin transporters. We also investigated POMC, 5-HT1B, and 5-HT2C protein levels. A single acute GbE dose induced the hypothalamic POMC, CART, and 5-HT2C gene expression but failed to modify orexigenic effectors. No alterations in food intake, body mass, and hypothalamic protein levels were observed. In summary, the present findings demonstrate the rapid stimulation of pivotal hypothalamic anorexigenic pathways in response to a single GbE administration, reinforcing the GbE hypophagic activity. However, more studies are necessary to evaluate its potential as an appetite modulator.

Keywords: food intake GbE; hypothalamic neuropeptides; serotonergic system.

Figure 1

Relative mRNA levels of the hypothalamic neuropeptides: POMC (a), CART (b), NPY (c), and AgRP (d) of Control (n = 5–6) and Ginkgo biloba (GbE; n = 5–6) groups analyzed by RT-qPCR. ** p < 0.01, *** p < 0.001.

Figure 2

Relative mRNA levels of the serotonin receptors and serotonin transporter: 5-HT1A (a), 5-HT1B (b), 5-HT2C (c), and 5HTT (d) of Control (n = 5–6) and Ginkgo biloba (GbE; n = 5–6) groups analyzed by RT-qPCR. * p < 0.05.

Figure 3

Relative mRNA levels of the leptin receptor (LEPr) in the hypothalamus. Control (n = 6) and Ginkgo biloba (GbE; n = 6) groups analyzed by RT-qPCR.

Figure 4

Hypothalamic protein expression. POMC (a), 5-HT1B (b), and 5-HT2C (c) of control (n = 4–6) and Ginkgo biloba (GbE; n = 6) groups.

Figure 5

Schematic diagram of the effect of GbE on energy homeostasis. Current results show the GbE effects on hypothalamic anorexigenic pathways, such as increasing the gene expression of 5-HT2C receptor and POMC/CART neuropeptides in normal male rats. The modulation of serotonergic pathways by GbE was also observed in ovariectomized rats with the reduction of the hypothalamic serotonin transporter (5-HTT), restoring the extracellular serotonin (5-HT) levels in the ventromedial hypothalamus as well as re-establishing the hippocampal levels of 5-HT1A and 5-HT1B serotonin receptors. This hippocampal activity together with the decrease in oxidative stress is likely involved in the improvement of depressive- and anxious-like behaviors observed in ovariectomized rats. Additionally, all these central modulations of GbE might have led to the reduction of food intake and body mass in both ovariectomized rats and diet-induced obese male rats. GbE hippocampal activity increased the leptin receptor levels, which participate in the negative feedback of feeding behavior and thus may be involved with the GbE hypophagic effect. Moreover, the GbE central effects might have also favored other responses previously described in diet-induced obese rats, such as the regulation of proteins involved in lipid metabolism, inflammation, and oxidative stress in the retroperitoneal fat depot, as well as the increase of insulin signaling and sensitivity, observed in both the white adipose tissue and gastrocnemius muscle. GbE also reduced the visceral adiposity with a decrease of adipocyte volume, synthesis, and incorporation of fatty acid into triacylglycerol in epididymal adipose tissue.