Üridinin nesfatin-1, oreksin-A ve leptin seviyeleri üzerine etkileri

Giriş ve Amaç: Günümüzde hızla artan obezite sorunu nedeniyle gıda alımının kontrolünü sağlayan molekül ve yolaklar ile ilgili araştırmaların önemi giderek artmaktadır. İnsan dolaşımındaki temel pirimidin nükleozidi olan üridinin açlık ve gıda alımının dinamik olarak düzenlenen bir aracısı olduğu gösterilmiştir (1). Gıda alımını baskılayan Nesftatin-1 (2) ve arttıran Oreksin-A (3) beslenmenin düzenlenmesinde önemli iki peptittir. Leptin ise beyaz adipoz dokudan dolaşıma salgılanıp beyne taşınmakta ve iştah ve vücut ağırlığında azalmaya sebep olmaktadır (4). Gereç ve Yöntem: Çalışmamızda 14 adet 8-12 haftalık Sprague-Dawley cinsi erkek sıçan kullanılmıştır. Randomize olarak 2 gruba ayrılan sıçanlara 4 gün boyunca serum fizyolojik (Kontrol grubu, n=7) veya üridin (Üridin grubu, 500 mg/kg, n=7) intraperitoneal olarak uygulanmıştır. Hayvanlar her gün tartılmıştır ve vücut ağırlıkları not edilmiştir. Deney ardından retro-orbital olarak alınan kan örneklerinden elde edilen serumlardan Nesfatin-1, Oreksin-A ve Leptin seviyeleri ELISA yöntemi ile analiz edilmiştir. Bulgular ve Sonuç: Sonuçlara bakıldığında Kontrol grubuna göre Üridin grubundaki hayvanların vücut ağırlığı değişim yüzdesinin daha fazla olduğu gözlenmiştir. Kontrol grubuna göre Üridin grubunda serum Nesfatin-1 seviyeleri anlamlı olarak azalırken Oreksin-A seviyeleri anlamlı olarak artmış ancak Leptin seviyelerinde anlamlı bir fark saptanmamıştır. Bu çalışma ile üridinin gıda alımı ve vücut ağırlığını düzenlemede önemli bir aracı olduğu, bu etkileri de leptin dışı yolaktan Nesfatin-1 seviyesini azaltarak ve Oreksin-A seviyesini arttırak yaptığı gösterilmiştir. Kaynakça: Kaynakça: 1. Hanssen, R., Rigoux, L., Albus, K., Kretschmer, A. C., Edwin Thanarajah, S., Chen, W., Hinze, Y., Giavalisco, P., Steculorum, S. M., Cornely, O. A., Brüning, J. C., & Tittgemeyer, M. (2023). Circulating uridine dynamically and adaptively regulates food intake in humans. Cell Reports Medicine, 4(1). https://doi.org/10.1016/j.xcrm.2022.100897. 2. Oh-I, S., Shimizu, H., Satoh, T., Okada, S., Adachi, S., Inoue, K., Eguchi, H., Yamamoto, M., Imaki, T., Hashimoto, K., Tsuchiya, T., Monden, T., Horiguchi, K., Yamada, M., & Mori, M. (2006). Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature, 443(7112), 709–712. https://doi.org/10.1038/nature05162. 3. De Lecea, L., Kilduff, T. S., Peyron, C., Gao, X. B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., Frankel, W. N., Van Den Pol, A. N., Bloom, F. E., Gautvik, K. M., & Sutcliffe, J. G. (1998). The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity. Proceedings of the National Academy of Sciences of the United States of America, 95(1), 322–327. https://doi.org/10.1073/pnas.95.1.322. 4. Ahlma, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature, 382(6588), 250–252. https://doi.org/10.1038/382250a0.

Anahtar Kelimeler:

Üridin, Nesfatin-1, Oreksin-A, Leptin

Effects of uridine on nesfatin-1, orexin-A and leptin levels

Aim: Due to the rapidly increasing obesity problem, studies on molecules and pathways that control food intake are becoming important. Uridine, the main pyrimidine nucleoside in the human circulation, has been shown to be a dynamically regulated mediator of hunger and food intake (1). Nesftatin-1, which suppresses food intake (2), and Orexin-A (3) which increases appetite, are important peptides for regulation of nutrition. Leptin is secreted into the circulation from white adipose tissue and transported to the brain, causing a decrease in appetite and body weight (4). Material and Methods: In this study, 8-12 week-old, Sprague-Dawley male rats were used (n=14). The rats were randomized into 2 groups: saline (Control group, n=7) or uridine (Uridine group, 500mg/kg, n=7) was administered intraperitoneally for 4 days. The animals were weighed daily. After the experiment, blood samples were obtained retro-orbitally and the serum levels of Nesfatin-1, Orexin-A and Leptin were analyzed by ELISA method. Results and Conclusion: When the results were examined, it was observed that the percentage of body weight change was higher in the Uridine group compared to the Control group. While serum Nesfatin-1 levels decreased, Orexin-A levels increased significantly in the Uridine group compared to the Control group. No significant difference was found in serum Leptin levels. In this study, it was shown that uridine is an important mediator in regulating food intake and body weight, and that it exerts these effects by decreasing the level of Nesfatin-1 from the non-leptin pathway and increasing the level of Orexin-A. References: Kaynakça: 1. Hanssen, R., Rigoux, L., Albus, K., Kretschmer, A. C., Edwin Thanarajah, S., Chen, W., Hinze, Y., Giavalisco, P., Steculorum, S. M., Cornely, O. A., Brüning, J. C., & Tittgemeyer, M. (2023). Circulating uridine dynamically and adaptively regulates food intake in humans. Cell Reports Medicine, 4(1). https://doi.org/10.1016/j.xcrm.2022.100897. 2. Oh-I, S., Shimizu, H., Satoh, T., Okada, S., Adachi, S., Inoue, K., Eguchi, H., Yamamoto, M., Imaki, T., Hashimoto, K., Tsuchiya, T., Monden, T., Horiguchi, K., Yamada, M., & Mori, M. (2006). Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature, 443(7112), 709–712. https://doi.org/10.1038/nature05162. 3. De Lecea, L., Kilduff, T. S., Peyron, C., Gao, X. B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., Frankel, W. N., Van Den Pol, A. N., Bloom, F. E., Gautvik, K. M., & Sutcliffe, J. G. (1998). The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity. Proceedings of the National Academy of Sciences of the United States of America, 95(1), 322–327. https://doi.org/10.1073/pnas.95.1.322. 4. Ahlma, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature, 382(6588), 250–252. https://doi.org/10.1038/382250a0.

Keywords:

Uridine, Nesfatin-1, Orexin-A, Leptin,

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