Santral Kisspeptin Uygulaması, Serum Ghrelin ve Oreksin A Düzeylerini Etkilerken Leptin Üzerinde Etki Göstermemektedir: CRH ve Oksitosin/Vazopressin Yollaklarıyla Etkileşimilerini

Year 2025, Volume: 6 Issue: 3, 235 - 242, 28.09.2025

Ömer Faruk Kalkan , Ali Yavuz Uzun , Fatmanur Selim , Abdullah Kaan Kurt , Şeniz Erdem , Elif Şahin , Ahmet Alver , Zafer Şahin

https://doi.org/10.47482/acmr.1681811

Abstract

Amaç
KISS1 geni tarafından kodlanan nöropeptitler olan kisspeptinler, hipotalamus-hipofiz-gonad (HPG) aksının düzenlenmesinde kritik bir rol oynamakta olup, metabolik düzenleme, enerji dengesi ve beslenme davranışıyla ilişkili süreçlerdede rol almaktadır. Ancak besleneme sürcinde, kisspeptinin, leptin, ghrelin ve oreksin A gibi temel metabolik peptitler üzerindeki etkilerine dair mekanizmalar hâlâ tam olarak aydınlatılamamıştır. Bu çalışma, kisspeptinin metabolik etkilerini inceleyerek, stresle ilişkili nöropeptitler olan kortikotropin salgılatıcı hormon (CRH), adrenokortikotropik hormon (ACTH), oksitosin ve vazopressin ile olan etkileşimlerini araştırmaktadır.
Yöntem
Sıçanlar rastgele yedi gruba ayrıldı (her grup için n = 10): Sham (kontrol), Kisspeptin (50 pmol), P234 (1 nmol), Kisspeptin + P234, Kisspeptin + Antalarmin (0.1 µg), Kisspeptin + Astressin 2B (1 µg), ve Kisspeptin + Atosiban (300 ng). Tüm uygulamalar intrasebroventriküler (ICV) enjeksiyon yoluyla gerçekleştirildi. Sıçanlar üretan (1.25 g/kg, i.p.) ile anestezi altına alındı. Uygulamadan 30 dakika sonra dekapitasyonla serum örnekleri alındı ve oreksin A, ghrelin ve leptin düzeyleri ticari ELISA kitleri ile ölçüldü.
Bulgular
Tek başına uygulanan kisspeptin, plazma leptin düzeylerinde anlamlı bir değişiklik oluşturmadı (p > 0.05). Ancak, kisspeptin serum ghrelin düzeylerini anlamlı şekilde azalttı (p < 0.05). Kisspeptinin P234, antalarmin, astressin 2B veya atosiban ile birlikte uygulanması ghrelin düzeylerinde artışa yol açtı (p < 0.05). Oreksin A açısından ise, tek başına kisspeptin uygulaması serum düzeylerini değiştirmezken; P234 veya antalarmin ile birlikte uygulanması oreksin A düzeylerini anlamlı şekilde artırdı (p < 0.05).
Sonuç
Bu çalışmanın verileri, kisspeptinin metabolik etkilerine dair yeni bulgular sunmakta olup, ghrelin salınımını baskıladığını ve CRH reseptör yolları aracılığıyla oreksin A düzeylerini modüle ettiğini göstermektedir.

Keywords

Kisspeptin , leptin , ghrelin , orexin A , p234

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

Abstract

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 <0.05). Regarding orexin-A, kisspeptin alone did not alter serum levels; however, co-administration with P234 (135 pg/ml) or antalarmin (165 pg/ml) significantly increased orexin-A levels (p < 0.05).
Conclusion: This study shows for the first time the metabolic effects of kisspeptin, demonstrating its role in suppressing ghrelin secretion and modulating orexin-A levels through CRH receptor pathways.

Keywords

Kisspeptin , leptin , ghrelin , orexin A , p234

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