Evaluation of Orexin A and Orexin B Levels after Bariatric Surgery in Patient with Obesity

Öz

Abstract: This study aimed to evaluate the changes in serum Orexin A and B levels following laparoscopic sleeve gastrectomy (LSG) in patients with obesity. Methods: Thirty obese patients undergoing LSG were evaluated at baseline, 3 months, and 6 months postoperatively for Orexin A and B levels and BMI. Results: A significant reduction in BMI was observed at postoperative 3 and 6 months (p < 0.001). Orexin B levels significantly declined at 6 months compared to preoperative and 3-month values (p = 0.002), while changes in Orexin A were not statistically significant. No correlation was found between orexin levels and BMI. Conclusions: Postoperative reductions in Orexin B may reflect a role in appetite regulation following bariatric surgery. These findings support further investigation into orexin-targeted therapies in obesity management. Methods: Preoperative, postoperative 3rd, and 6th-month venous blood samples were collected from 30 obese patients diagnosed with obesity and undergoing LSG to measure Orexin A and B levels. The obtained values and body maSD indexes (BMI) calculated at the same time intervals were compared. This study was approved by the Clinical Research Ethics Committee of the University of Health Sciences Antalya Training and Research Hospital (Approval Date: August 5, 2021; Approval No: 11/10) and was conducted in accordance with the Declaration of Helsinki. Conclusions: Previous experimental studies have shown that Orexin peptides are activated in the fasting state and play an active role in obesity by increasing food intake. In this study, we found that Orexin B levels were significantly reduced in patients who experienced weight loss. We believe that monitoring Orexin levels can be beneficial in the treatment of obesity, and inhibiting its activity at the hypothalamic level can contribute to the treatment by reducing food intake. Conducting new studies with a larger number of patients and longer follow-up periods will lead to radical and effective changes in the treatment of obesity.

Anahtar Kelimeler

• bariatric surgery
• body maSD index
• laparoscopic sleeve gastrectomy
• Orexin A
• Orexin B

Obez Hastalarda Bariatrik Cerrahi Sonrası Oreksin A ve Oreksin B Düzeylerinin Değerlendirilmesi

Öz

Amaç: Bu çalışma, obezite hastalarında uygulanan laparoskopik sleeve gastrektomi (LSG) sonrası serum Oreksin A ve B düzeylerindeki değişimleri değerlendirmeyi amaçlamıştır. Yöntem: LSG uygulanan 30 obez hastada, preoperatif, postoperatif 3. ay ve 6. ay dönemlerinde Oreksin A ve B düzeyleri ile vücut kitle indeksi (VKİ) değerlendirildi. Bulgular: Postoperatif 3. ve 6. aylarda VKİ’de anlamlı bir azalma gözlemlendi (p < 0.001). Oreksin B düzeyleri, preoperatif ve 3. ay değerlerine kıyasla 6. ayda anlamlı şekilde azaldı (p = 0.002). Oreksin A düzeylerinde istatistiksel olarak anlamlı bir değişiklik saptanmadı. Oreksin düzeyleri ile VKİ arasında anlamlı bir korelasyon bulunmadı. Sonuç: Postoperatif dönemde Oreksin B düzeylerindeki azalma, bariyatrik cerrahi sonrası iştah düzenlemesinde rol oynayabileceğini düşündürmektedir. Bu bulgular, obezite tedavisinde oreksin hedefli tedavilerin daha fazla araştırılmasını desteklemektedir. Yöntem Detayı: Obezite tanısı almış ve LSG uygulanan 30 hastadan, preoperatif, postoperatif 3. ve 6. aylarda venöz kan örnekleri alınarak Oreksin A ve B düzeyleri ölçüldü. Aynı zaman aralıklarında hesaplanan vücut kitle indeksi (VKİ) ile birlikte elde edilen veriler karşılaştırıldı. Etik Onay: Çalışma, SBÜ Antalya Eğitim ve Araştırma Hastanesi Klinik Araştırmalar Etik Kurulu tarafından onaylanmıştır (Onay Tarihi: 5 Ağustos 2021; Onay No: 11/10) ve Helsinki Deklarasyonu’na uygun şekilde yürütülmüştür. Geniş Sonuç Yorumu: Önceki deneysel çalışmalar, Oreksin peptitlerinin açlık durumunda aktive olduğunu ve gıda alımını artırarak obezitede aktif rol oynadığını göstermiştir. Bu çalışmada, kilo kaybı yaşayan hastalarda Oreksin B düzeylerinde anlamlı bir azalma saptanmıştır. Oreksin düzeylerinin takibinin obezite tedavisinde faydalı olabileceği, hipotalamik düzeyde aktivitesinin baskılanmasının gıda alımını azaltarak tedaviye katkı sağlayabileceği düşünülmektedir. Daha fazla hasta içeren ve uzun takip sürelerine sahip yeni çalışmaların yapılması, obezite tedavisinde köklü ve etkili gelişmelere yol açabilir.

Anahtar Kelimeler

• bariyatrik cerrahi
• vücut kitle indeksi
• laparoskopik sleeve gastrektomi
• Oreksin A
• Oreksin B

Kaynakça

1. 1. Lin X, Li H. Obesity: epidemiology, pathophysiology, and therapeutics. Front Endocrinol (Lausanne). 2021;12:706978. Crossref
2. 2.Garrow JS, Webster J. Quetelet's index (W/H²) as a measure of fatness. Int J Obes. 1985;9:147-53.
3. 3.Scherer PE, Hill JA. Obesity, diabetes, and cardiovascular diseases: a compendium. Circ Res. 2016;118:1703-5. Crossref
4. 4.Hruby A, Hu FB. The epidemiology of obesity: a big picture. Pharmacoeconomics. 2015;33:673-89. Crossref
5. 5.Murshid KR, Alsisi GH, Almansouri FA, Zahid MM, Boghdadi AA, Mahmoud EH. Laparoscopic sleeve gastrectomy for weight loss and treatment of type 2 diabetes mellitus. J Taibah Univ Med Sci. 2021;16:387-94. Crossref
6. 6.Chieffi S, Carotenuto M, Monda V, Valenzano A, Villano I, Precenzano F, et al. Orexin system: the key for a healthy life. Front Physiol. 2017;8:357. Crossref
7. 7.Mogavero MP, Silvani A, Lanza G, DelRosso LM, Ferini-Strambi L, Ferri R. Targeting orexin receptors for the treatment of insomnia: from physiological mechanisms to current clinical evidence and recommendations. Nat Sci Sleep. 2023;15:17-38. Crossref
8. 8.Cason AM, Smith RJ, Tahsili-Fahadan P, Moorman DE, Sartor GC, Aston-Jones G. Role of orexin/hypocretin in reward-seeking and addiction: implications for obesity. Physiol Behav. 2010;100:419-28. Crossref

9. 9.Jöhren O, Neidert SJ, Kummer M, Dendorfer A, Dominiak P. Prepro-orexin and orexin receptor mRNAs are differentially expressed in peripheral tissues of male and female rats. Endocrinology. 2001;142:3324-31. Crossref
10. 10.Barson JR. Orexin/hypocretin and dysregulated eating: promotion of foraging behavior. Brain Res. 2020;1731:145915. Crossref
11. 11.de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95:322-7. Crossref
12. 12.Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92:573-85. Crossref
13. 13.Sakurai T, Mieda M, Tsujino N. The orexin system: roles in sleep/wake regulation. Ann N Y Acad Sci. 2010;1200:149-61. Crossref
14. 14.Teske JA, Mavanji V. Energy expenditure: role of orexin. Vitam Horm. 2012;89:91-109. Crossref
15. 15.Inutsuka A, Yamanaka A. The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions. Front Endocrinol (Lausanne). 2013;4:18. Crossref
16. 16.Haynes AC, Jackson B, Chapman H, Tadayyon M, Johns A, Porter RA, et al. A selective orexin-1 receptor antagonist reduces food consumption in male and female rats. Regul Pept. 2000;96:45-51. Crossref
17. 17.Shiraishi T, Oomura Y, Sasaki K, Wayner MJ. Effects of leptin and orexin-A on food intake and feeding-related hypothalamic neurons. Physiol Behav. 2000;71:251-61. Crossref
18. 18.Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, et al. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron. 2003;38:701-13. Crossref
19. 19.Digby JE, Chen J, Tang JY, Lehnert H, Matthews RN, Randeva HS. Orexin receptor expression in human adipose tissue: effects of orexin-A and orexin-B. J Endocrinol. 2006;191:129-36. Crossref
20. 20.Sakurai T. The role of orexin in motivated behaviours. Nat Rev Neurosci. 2014;15:719-31. Crossref
21. 21.Kotz CM, Perez-Leighton CE, Teske JA, Billington CJ. Spontaneous physical activity defends against obesity. Curr Obes Rep. 2017;6:362-70. Crossref
22. 22.Funato H, Tsai AL, Willie JT, Kisanuki Y, Williams SC, Sakurai T, et al. Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metab. 2009;9:64-76. Crossref
23. 23.Kakizaki M, Tsuneoka Y, Takase K, Kim SJ, Choi J, Ikkyu A, et al. Differential roles of each orexin receptor signaling in obesity. iScience. 2019;20:1-13. Crossref
24. 24.Luo N, Liu J, Chung BH, Yang Q, Klein RL, Garvey WT, et al. Macrophage adiponectin expression improves insulin sensitivity and protects against inflammation and atherosclerosis. Diabetes. 2010;59:791-9. Crossref
25. 25.Rejdak K, Papuć E, Grieb P, Stelmasiak Z. Decreased cerebrospinal fluid hypocretin-1 (orexin A) in patients after repetitive generalized tonic-clonic seizures. Epilepsia. 2009;50:1641-4. Crossref
26. 26.Han Y, Yuan K, Zheng Y, Lu L. Orexin receptor antagonists as emerging treatments for psychiatric disorders. Neurosci Bull. 2020;36:432-48. Crossref
27. 27.James MH, Stopper CM, Zimmer BA, Koll NE, Bowrey HE, Aston-Jones G. Increased number and activity of a lateral subpopulation of hypothalamic orexin/hypocretin neurons underlies the expression of an addicted state in rats. Biol Psychiatry. 2019;85:925-35. Crossref
28. 28.Baumann CR, Bassetti CL. Hypocretins (orexins): clinical impact of the discovery of a neurotransmitter. Sleep Med Rev. 2005;9:253-68. Crossref
29. 29.Morris CJ, Aeschbach D, Scheer FA. Circadian system, sleep and endocrinology. Mol Cell Endocrinol. 2012;349:91-104. Crossref
30. 30.Terrill SJ, Hyde KM, Kay KE, Greene HE, Maske CB, Knierim AE, et al. Ventral tegmental area orexin-1 receptors promote palatable food intake and oppose postingestive negative feedback. Am J Physiol Regul Integr Comp Physiol. 2016;311:R592-9. Crossref
31. 31.Tsujino N, Sakurai T. Role of orexin in modulating arousal, feeding, and motivation. Front Behav Neurosci. 2013;7:28. Crossref
32. 32.Blais A, Drouin G, Chaumontet C, Voisin T, Couvelard A, Even PC, et al. Impact of orexin-A treatment on food intake, energy metabolism and body weight in mice. PLoS One. 2017;12:e0169908. Crossref
33. 33.Liu L, Wang Q, Liu A, Lan X, Huang Y, Zhao Z, et al. Physiological implications of orexins/hypocretins on energy metabolism and adipose tissue development. ACS Omega. 2019;5:547-55. Crossref
34. 34.Grafe LA, Bhatnagar S. Orexins and stress. Front Neuroendocrinol. 2018;51:132-45. Crossref