TY - JOUR T1 - İntraserebroventriküler Nesfatin-1 Enjeksiyonun Erkek Sıçanlarda Serum Ghrelin Leptin, Orexin A ve Asprosin Düzeylerine Etkisi TT - The Effect of Intracerebroventricular Nesfatin-1 Injection on Serum Ghrelin, Leptin, Orexin A, and Asprosin Levels in Male Rats AU - Kalkan, Ömer Faruk AU - Selim, Fatmanur AU - Uzun, Ali Yavuz AU - Alver, Ahmet AU - Şahin, Zafer PY - 2025 DA - September Y2 - 2025 DO - 10.37989/gumussagbil.1728090 JF - Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi JO - Gümüşhane Sağlık Bilimleri Dergisi PB - Gumushane University WT - DergiPark SN - 2146-9954 SP - 878 EP - 885 VL - 14 IS - 3 LA - tr AB - Hipotalamik alanlarda üretilen nesfatin-1 anoreksijenik bir peptittir. Nesfatin-1’in bu anoreksijenik etkisinde hipotalamo-hipofizer-adrenal aks aktivasyonu yanı sıra stres yanıtı da rol oynar. Nesfatin-1’in leptin, ghrelin, orexin-A ve asprosin gibi açlık-tokluk üzerinde önemli rol oyanayan nöropeptitler üzerinde nasıl bir etkiye sahip olduğu tam olarak aydınlatılmamıştır. Bu çalışmada, nesfatin-1’in CRH1, CRH2 ve oksitosin reseptör antagonistleriyle etkileşiminin, serum ghrelin, leptin, asprosin ve oreksin A düzeyleri üzerindeki etkilerini araştırmak hedeflenmiştir.Çalışmada toplam 42 adet erkek sıçan kullanılmış ve rastgele 6 gruba ayrılmıştır; (her grup için n=7): sham (kontrol), nesfatin-1, nesfatin-1 (25pmol) +P234 (1 nmol), nesfatin-1+antalarmin (0,1 μg), nesfatin-1+ astressin (1 μg) 2B, nesfatin-1+atosiban (300 ng). Tüm antagonistler introserebroventriküler yolla enjekte edilmiştir. Hayvanlar anestezi (1.25 g/kg, periton içi) altına alındıktan 30 dakika sonra dekapitasyonla sakrifiye edilmiştir. Serum örnekleri toplanmış ve leptin, ghrelin, orexin A ve asprosin seviyeleri ELISA ticari kitleri ile ölçülmüştür.Nesfatin-1’ tek başına uygulaması serum leptin, ghrelin, orexin-A ve asprosin seviyelerini değiştirmemiştir (p>0.05). Nesfatin-1’in P234 ile uygulaması orexin-A ve ghrelin seviyelerini azaltırken leptin seviyesini artırmıştır (p KW - Nesfatin-1 KW - Ghrelin KW - Leptin KW - Oreksin A KW - Asprosin N2 - Nesfatin-1 is an anorexigenic peptide produced in hypothalamic regions. The anorexigenic effect of nesfatin-1 involves not only the activation of the hypothalamic-pituitary-adrenal (HPA) axis but also the stress response. Although nesfatin-1 is known to influence appetite-regulating neuropeptides, its specific effects on leptin, ghrelin, orexin-A, and asprosin have yet to be fully characterized. This study was conducted to explore how nesfatin-1 interacts with CRH1, CRH2, and oxytocin receptor antagonists to affect the serum concentrations of these neuropeptides.In this study, a total of 35 animals were used and randomly divided into 5 groups (n=7 per group): sham (control), nesfatin-1, nesfatin-1 (25 pmol) + P234 (1 nmol), nesfatin-1 + antalarmin (0.1 μg), nesfatin-1 + astressin 2B (1 μg), and nesfatin-1 + atosiban (300 ng). All antagonists were administered via the intracerebroventricular route. The animals were sacrificed by decapitation 30 minutes after anesthesia (1.25 g/kg, intraperitoneal). Serum samples were collected, and levels of leptin, ghrelin, orexin A, and asprosin were measured using commercial ELISA kits.Administration of nesfatin-1 alone did not significantly alter serum leptin, ghrelin, orexin-A, or asprosin levels (p>0.05). Co-administration of nesfatin-1 with P234 reduced orexin-A and ghrelin levels while increasing leptin levels (p CR - 1. Zhu XX, Meng XY, Chen G, et al. Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling. Cell Commun Signal. 2024;22(1):488. CR - 2. Dore R, Levata L, Lehnert H, Schulz C. Nesfatin-1: functions and physiology of a novel regulatory peptide. J Endocrinol. 2017;32(1):45-65. CR - 3. Oh-I S, Shimizu H, Satoh T, Okada S, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. 2006;443(7112):709-12. CR - 4. Price CJ, Hoyda TD, Samson WK, et al. Nesfatin-1 influences the excitability of paraventricular nucleus neurones. J Neuroendocrinol. 2008;20(2):245-50. CR - 5. Price CJ, Samson WK, Ferguson AV. Nesfatin-1 inhibits NPY neurons in the arcuate nucleus. Brain Res. 2008;16(1230):99-106. CR - 6. Nakata M, Gantulga D, Santoso P, et al. Paraventricular NUCB2/nesfatin-1 supports oxytocin and vasopressin neurons to control feeding behavior and fluid balance in male mice. Endocrinology. 2016;157(6):2322-32. CR - 7. Stengel A, Goebel M, Wang L, et al. Central nesfatin-1 reduces dark-phase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor. Endocrinology. 2009(150):4911-9. CR - 8. Güldemir, H. Yüksek yağlı diyetin açlık-tokluk metabolizmasında görevli hormonlar ve nöropeptidler üzerine etkileri. Sağlık Bilimleri Dergisi. 2018;27(3):239-344. CR - 9. Pereira S, Cline DL, Glavas MM, et al. Tissue-specific effects of leptin on glucose and lipid metabolism. Endocr Rev. 2021;42(1):1-28. CR - 10. Gray SM, Page LC, Tong J. Ghrelin regulation of glucose metabolism. J Neuroendocrinol. 2019;31(7):2705. 11. Li E, Shan H, Chen L, et al. OLFR734 mediates glucose metabolism as a receptor of asprosin. Cell Metab. 2019;30(2):319-328. CR - 12. Xia L, Liu HY, Wang BY, et al. A review of physiological functions of orexin: From instinctive responses to subjective cognition. Medicine (Baltimore). 2023;102(26):34206. CR - 13. G. Cristina Brailoiu, Siok L. Dun, Eugen Brailoiu, et al. Nesfatin-1: sıçan beyninde g protein bağlantılı reseptörle dağılım ve etkileşim. Endokrinoloji. 2007;148(10):5088-509. CR - 14. Gotoh K, Masaki T, Chiba S, et al. Nesfatin-1, corticotropin-releasing hormone, thyrotropin-releasing hormone, and neuronal histamine interact in the hypothalamus to regulate feeding behavior. J Neurochem 2013;124(1):90-9. CR - 15. Bagosi Z, Csabafi K, Palotai M, et al. The effect of urocortin I on the hypothalamic ACTH secretagogues and its impact on the hypothalamic-pituitary-adrenal axis. Neuropeptides. 2014;48(1):15-20. CR - 16. Benoussaidh A, Maurin Y, Rampin O. Possible neural mediation of the central effects of oxytocin on uterine motility. Am J Physiol Regul Integr Comp Physiol 2005;289(3):798-804. CR - 17. Pan W, Hsuchou H, Kastin A J. Nesfatin-1 crosses the blood-brain barrier without saturation. Peptides. 2007;28(11):2223-8. CR - 18. Paxinos, G, Watson, C. The Rat Brain in Stereotaxic Coordinates, 6th edn. Journal of Anatomy. New York: Academic Press. CR - 19. Darambazar G, Nakata M, Okada T, et al. Paraventricular NUCB2/nesfatin-1 is directly targeted by leptin and mediates its anorexigenic effect. Biochem Biophys Res Commun. 2015;456(4):913-8. CR - 20. Çelik F, Belviranli M, Okudan N. Circulating levels of leptin, nesfatin-1 and kisspeptin in postmenopausal obese women . Arch Physiol Biochem. 2016; 122(4):195-199 CR - 21. Li ZL, Xu L, Sun XR, Guo FF, Gong YL, Gao SL (2013). Central nesfatin-1 influences the excitability of ghrelin-responsive gastric distension neurons in the arcuate nucleus and reduces gastric motility in rats. Eur J Neurosci 38:3636-43. CR - 22. Inhoff T, Mönnikes H, Noetzel S, Stengel A, Goebel M, Dinh QT, Riedl A, Bannert N, Wisser AS, Wiedenmann B, Klapp BF, Taché Y, Kobelt P (2008). Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats. Peptides 29:2159-68. CR - 23. Gök Yurtseven D, Minbay Z, Eyigör Ö (2019). Nesfatin-1 ve oreksin a nöronları arasındaki etkileşimin immünohistokimyasal olarak araştırılması. Uludağ Tıp Derg. 45: 243-249. UR - https://doi.org/10.37989/gumussagbil.1728090 L1 - https://dergipark.org.tr/en/download/article-file/4994421 ER -