Central Kisspeptin Modulates Serum Ghrelin and Orexin A Levels Without Affecting Leptin: Interactions with CRH and Oxytocin/Vasopressin Pathways

Background: Kisspeptins, neuropeptides encoded by the KISS1 gene, play a critical role in regulating the hypothalamic-pituitary-gonadal (HPG) axis and have emerging links to metabolic regulation, energy balance, and feeding behaviour. The precise mechanisms by which kisspeptin influences key metabolic peptides such as leptin, ghrelin, and orexin-A remain unclear. This study investigates the metabolic effects of kisspeptin, exploring its interactions with stress-related neuropeptides, including corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), oxytocin, and vasopressin. Methods: Rats were randomly divided into seven groups (n = 10 per group): Sham (control), Kisspeptin (50 pmol), P234 (1 nmol), Kisspeptin + p234 (1 nmol), Kisspeptin + Antalarmin (0.1 μg), Kisspeptin + astressin-2B (1 μg), and Kisspeptin + Atosiban (300 ng). All treatments were administered via intracerebroventricular (ICV) injection. Rats were anesthetized with urethane (1.25 g/kg, i.p.). Serum was collected by decapitation after 30 minutes, and levels of orexin-A, ghrelin and leptin were measured using commercial ELISA kits. Results: Kisspeptin administration alone did not significantly affect plasma leptin levels (p > 0.05). However, kisspeptin significantly reduced serum ghrelin levels (40% reduction) (p < 0.05). Co-administration of kisspeptin with p234 (1100 pg/ml), antalarmin (1400 pg/ml), astressin-2B (1050 pg/ml), or atosiban (900 pg/ml) resulted in elevated ghrelin levels (p