Vitamin D Eksikliği Olan Yeni Zelanda Beyaz Tavşanlarında Ghrelin ve Leptin Salınımındaki Değişikliklerin Belirlenmesi

Abstract

İştah açıcı bir hormon olan ghrelin, iştahı uyararak enerji alımını artırırken, iştah kesici bir hormon olan leptin ise gıda tüketimini bastırarak enerji dengesinin korunmasında hayati bir rol oynar. Bu çalışma, vitamin D eksikliği olan bir diyetle beslenen Yeni Zelanda Beyaz tavşanlarda vitamin D eksikliğini indüklemek için gereken süreyi belirlemeyi ve deneysel bir tavşan modeli kullanarak bu eksikliğin ghrelin-leptin ekseni yoluyla enerji dengesi üzerindeki etkilerini araştırmayı amaçlamıştır. Çalışmaya toplam on altı adet iki aylık Yeni Zelanda Beyaz tavşan dahil edilmiştir. 15 günlük bir alışma döneminin ardından, hayvanlar rastgele her biri sekiz tavşandan oluşan iki gruba ayrılmıştır. Grup II, vitamin D ile takviye edilmiş standart bir tavşan diyetiyle beslenirken, Grup I 24 haftalık bir süre boyunca vitamin D eksikliği olan bir diyetle beslenmiştir. Serum 25-hidroksivitamin D [25(OH)D] düzeyleri, Grup I'de 22,15 ± 1,70 ng/mL ve Grup II'de 44,20 ± 6,09 ng/mL olarak ölçüldü; bu da vitamin D eksikliğinin başarılı bir şekilde indüklendiğini doğruladı. Açlık ghrelin düzeyleri, Grup I'de 0,13 ± 0,02 ng/mL ve Grup II'de 0,24 ± 0,04 ng/mL olarak bulundu. Benzer şekilde, serum leptin düzeyleri Grup I'de 2,39 ± 0,07 ng/mL ve Grup II'de 2,69 ± 0,09 ng/mL olarak ölçüldü. Bu bulgular, D vitamini eksikliğinin hem ghrelin hem de leptin konsantrasyonlarındaki değişikliklerle ilişkili olduğunu göstermektedir.

Keywords

• D vitamini
• grelin
• leptin
• enerji dengesi
• iştah kontrolü

Supporting Institution

Bu çalışma, Kafkas Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Ofisi tarafından desteklenmiştir (Proje numarası: 2017-TS-77).

Project Number

2017-TS-77

Ethical Statement

Bu çalışma, Kafkas Üniversitesi Hayvan Deneyleri Etik Kurulu’nun onayı (KAÜ-HADYEK/2016-114) alınarak gerçekleştirilmiştir.

Thanks

Bu çalışmaya destek veren Kafkas Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Ofisi’ne (Proje numarası: 2017-TS-77) teşekkür ederiz.

Effects of Dietary Vitamin D Deficiency on Serum Ghrelin and Leptin Levels in New Zealand White Rabbits

Abstract

Ghrelin, an orexigenic hormone, promotes energy intake by stimulating appetite, whereas leptin, an anorexigenic hormone, plays a pivotal role in maintaining energy homeostasis by suppressing food consumption. The present study aimed to evaluate whether a 24-week vitamin D-deficient diet induces vitamin D deficiency in New Zealand White rabbits and to assess the associated changes in serum ghrelin and leptin levels. A total of sixteen two-month-old New Zealand White rabbits were included in the study. Following a 15-day acclimatization period, the animals were randomly divided into two groups, each consisting of eight rabbits. Group II received a standard rabbit diet supplemented with vitamin D, whereas Group I was fed a vitamin D–deficient diet for a period of 24 weeks. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured as 22.15 ± 1.70 ng/mL in Group I and 44.20 ± 6.09 ng/mL in Group II, confirming the successful induction of vitamin D deficiency. Serum ghrelin levels were found to be 0.13 ± 0.02 ng/mL in Group I and 0.24 ± 0.04 ng/mL in Group II. Similarly, serum leptin levels were measured at 2.39 ± 0.07 ng/mL in Group I and 2.69 ± 0.09 ng/mL in Group II. In Group 2, 25(OH)D, ghrelin and leptin levels were found to be statistically significantly higher than in Group 1 (p < 0.05).These findings suggest that vitamin D deficiency is associated with alterations in both ghrelin and leptin concentrations.

Keywords

• vitamin D
• ghrelin
• leptin
• energy homeostasis
• appetite control

Supporting Institution

This study was supported by Kafkas University Scientific Research Project Coordination Office (Project number: 2017-TS-77).

Project Number

2017-TS-77

Ethical Statement

This study was conducted following approval from the Kafkas University Animal Experimentation Ethics Committee(KAÜ-HADYEK/2016-114)

Thanks

We would like to thank the Kafkas University Scientific Research Project Coordination Office (Project number: 2017-TS-77) for supporting this study.

References

1. AlGhamdi, S., Alsulami, N., Khoja, S., Alsufiani, H., Tayeb, H. O., Alshaibi, H., & Tarazi, F. I. (2024). Serum Ghrelin and leptin concentrations in patients with major depressive disorder before and after supplementation with vitamin D3. Depression and Anxiety, 2024(1), 2057881. https://doi.org/10.1155/2024/2057881
2. Amrein, K., Scherkl, M., Hoffmann, M., Neuwersch-Sommeregger, S., Köstenberger, M., Tmava Berisha, A., ... & Malle, O. (2020). Vitamin D deficiency 2.0: an update on the current status worldwide. European Journal of Clinical Nutrition, 74(11), 1498-1513.
3. Berridge, M.J. (2017). Vitamin D deficiency and diabetes. Biochemical Journal, 474(8), 1321-1332. https://doi.org/10.1042/BCJ20170042
4. Biercewicz, M., Kwiatkowska, K., Kędziora-Kornatowska, K., Krintus, M., Ślusarz, R., & Ruszkowska-Ciastek, B. (2023). Significant interactions between adipokines and vitamin D combined with the estimated glomerular filtration rate: A geriatric case study. Journal of Clinical Medicine, 12(6), 2370. https://doi.org/10.3390/jcm12062370
5. Charoenngam, N., & Holick, M. F. (2020). Immunologic effects of vitamin D on human health and disease. Nutrients, 12(7), 2097. https://doi.org/10.3390/nu12072097
6. Christakos, S., Li, S., De La Cruz, J., & Bikle, D. D. (2019). New developments in our understanding of vitamin D metabolism, action and treatment. Metabolism, 98, 112-120. https://doi.org/10.1016/j.metabol.2019.06.010
7. De Martinis, M., Allegra, A., Sirufo, M. M., Tonacci, A., Pioggia, G., Raggiunti, M., ... & Gangemi, S. (2021). Vitamin D deficiency, osteoporosis and effect on autoimmune diseases and hematopoiesis: a review. International Journal of Molecular Sciences, 22(16), 8855. https://doi.org/10.3390/ijms22168855
8. Dinca, M., Serban, M. C., Sahebkar, A., Mikhailidis, D. P., Toth, P. P., Martin, S. S., ... & Banach, M. (2016). Does vitamin D supplementation alter plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials. Pharmacological Research, 107, 360-371. https://doi.org/10.1016/j.phrs.2016.03.035.

9. Esteves, P. J., Abrantes, J., Baldauf, H. M., BenMohamed, L., Chen, Y., Christensen, N., ... & Mage, R. (2018). The wide utility of rabbits as models of human diseases. Experimental & Molecular Medicine, 50(5), 1-10. https://doi.org/ 10.1038/s12276-018-0094-1
10. Hajimohammadi, M., Shab-Bidar, S., & Neyestani, T. R. (2017). Consumption of vitamin D-fortified yogurt drink increased leptin and ghrelin levels but reduced leptin to ghrelin ratio in type 2 diabetes patients: a single blind randomized controlled trial. European Journal of Nutrition, 56(6), 2029-2036.
11. Hao, L., Lu, A., Gao, H., Niu, J., Prabahar, K., Seraj, S. S., & Pan, Y. (2023). The effects of vitamin D on markers of glucose and obesity in postmenopausal women: a meta-analysis of randomized controlled trials. Clinical Therapeutics, 45(9), 913-920. https://doi.org/10.1016/j.clinthera.2023.07.009
12. Janoušek, J., Pilařová, V., Macáková, K., Nomura, A., Veiga-Matos, J., Silva, D. D. D., ... & Mladěnka, P. (2022). Vitamin D: sources, physiological role, biokinetics, deficiency, therapeutic use, toxicity, and overview of analytical methods for detection of vitamin D and its metabolites. Critical Reviews in Clinical Laboratory Sciences, 59(8), 517-554. https://doi.org/10.1080/10408363.2022.2070595
13. Juliaty, A., Putri, S. H., & Ganda, I. J. (2022). Leptin Level in Obese Children with Vitamin D Deficiency. Open Access. Macedonian Journal of Medical Sciences, 10(B), 1102-1106. https://doi.org/10.3889/oamjms.2022.8276
14. Kaneko, I., Sabir, M. S., Dussik, C. M., Whitfield, G. K., Karrys, A., Hsieh, J. C., ... & Jurutka, P. W. (2015). 1, 25‐Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D. The FASEB Journal, 29(9), 4023-4035. https://doi.org/10.1096/fj.14-269811
15. Kong, J., Chen, Y., Zhu, G., Zhao, Q., & Li, Y. C. (2013). 1, 25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue. Journal of Endocrinology, 216(2), 265-271. https://doi.org/10.1530/JOE-12-0344
16. Kupisz-Urbańska, M., Płudowski, P., & Marcinowska-Suchowierska, E. (2021). Vitamin D deficiency in older patients—problems of sarcopenia, drug interactions, management in deficiency. Nutrients, 13(4), 1247. https://doi.org/10.3390/nu13041247
17. Madhu, S. V., Aslam, M., Mishra, B. K., Gupta, A., & Jhamb, R. (2022). Association of 25 (OH) vitamin D and leptin in individuals with insulin resistance. Indian Journal of Endocrinology and Metabolism, 26(5), 435-438. https://doi.org/10.4103/ijem.ijem_141_22
18. Mäkitaipale, J., Hietanen, P., & Grönthal, T. (2024). Low 25-hydroxyvitamin D concentrations in wild rabbits (Oryctolagus cuniculus) in southern Finland. Acta Veterinaria Scandinavica, 66(1), 4. https://doi.org/10.1186/s13028-024-00726-0
19. Mäkitaipale, J., Sankari, S., Sievänen, H., & Laitinen-Vapaavuori, O. (2020). The relationship between serum 25-hydroxyvitamin D and parathyroid hormone concentration in assessing vitamin D deficiency in pet rabbits. BMC Veterinary Research, 16(1), 403. https://doi.org/10.1186/s12917-020-02599-7
20. Menendez, C., Lage, M., Peino, R., Baldelli, R., Concheiro, P., Dieguez, C., & Casanueva, F. F. (2001). Retinoic acid and vitamin D3 powerfully inhibit in vitro leptin secretion by human adipose tissue. Journal of Endocrinology, 170(2), 425-432.
21. Mousa, A., Naderpoor, N., Wilson, K., Plebanski, M., de Courten, M. P., Scragg, R., & de Courten, B. (2020). Vitamin D supplementation increases adipokine concentrations in overweight or obese adults. European Journal of Nutrition, 59(1), 195-204.
22. Pál, É., Ungvári, Z., Benyó, Z., & Várbíró, S. (2023). Role of vitamin D deficiency in the pathogenesis of cardiovascular and cerebrovascular diseases. Nutrients, 15(2), 334. https://doi.org/10.3390/nu15020334
23. Rahme, M., Al-Shaar, L., Tamim, H., & El-Hajj Fuleihan, G. (2024). Blood pressure decreases in overweight elderly individuals on vitamin D: a randomized trial. Journal of the Endocrine Society, 8(12), bvae168. https://doi.org/10.1210/jendso/bvae168
24. Remelli, F., Vitali, A., Zurlo, A., & Volpato, S. (2019). Vitamin D deficiency and sarcopenia in older persons. Nutrients, 11(12), 2861. https://doi.org/10.3390/nu11122861
25. Sisley, S. R., Arble, D. M., Chambers, A. P., Gutierrez-Aguilar, R., He, Y., Xu, Y., ... & Sandoval, D. A. (2016). Hypothalamic vitamin D improves glucose homeostasis and reduces weight. Diabetes, 65(9), 2732-2741. https://doi.org/10.2337/db16-0309
26. Su, H., Liu, N., Zhang, Y., & Kong, J. (2021). Vitamin D/VDR regulates peripheral energy homeostasis via central renin-angiotensin system. Journal of Advanced Research, 33, 69-80. https://doi.org/10.1016/j.jare.2021.01.011
27. Voiculescu, V. M., Nelson Twakor, A., Jerpelea, N., & Pantea Stoian, A. (2025). Vitamin D: beyond traditional roles—insights into its biochemical pathways and physiological impacts. Nutrients, 17(5), 803.
28. Wimalawansa, S. J. (2023). Physiological basis for using vitamin D to improve health. Biomedicines, 11(6), 1542. https://doi.org/10.3390/biomedicines11061542.
29. Wimalawansa, S. J. (2024). Physiology of vitamin D—focusing on disease prevention. Nutrients, 16(11), 1666. https://doi.org/10.3390/nu16111666.