Böbreküstü Bezinde HMGB1 ile Obezite İlişkisinin Araştırılması

Yıl 2022, Cilt: 4 Sayı: 2, 242 - 50, 01.05.2022

Muhammed Erdal Zuhal Altunkaynak , Adem Kocaman , İşınsu Alkan , Emin Öztaş

https://doi.org/10.37990/medr.1087598

Cited By: 1

Öz

Amaç: Obezite ile artan proinflamatuar sitokin üretimi arasındaki etkileşim sonucu inflamasyonun varlığı adrenal bezden salgılanan HMGB1 inflamasyon yolaklarında rol oynayabilir. Bu çalışmanın amacı, adrenal bezde HMGB1 ile obezite arasındaki bağlantıyı açıklamaktır.
Materyal ve Metot: Bu çalışmada; on sekiz dişi Wistar Albino sıçanı tedavi edilmeyen kontrol grubu (n=8) ve obez grup (n=10) olmak üzere iki gruba ayrıldı. Obez gruptaki ratlar on hafta süreyle yüksek yağlı diyetle beslenirken, control grubu standart diyet ile beslendi. Adrenal bezin morfometrik parametreleri ve mobilite grubu kutu protein 1 (HMGB1) ekspresyonu stereolojik teknikler kullanılarak değerlendirildi.
Bulgular: Analizler sonunda; zona fasikülata, zona retikülaris ve medulla ortalama hacimlerinim obez grupta anlamlı olarak arttığı görüldü. Ayrıca obez grupta HMGB1 ile boyanmış hücre sayısı kontrol grubuna göre önemli ölçüde artmıştı.
Sonuç: Sonuçlar obezitenin adrenal bezdeki inflamasyon ve hipertrofi nedenlerinden biri olabileceğini düşündürmektedir. HMGB1, obez hastalarda anti-inflamatuar terapötik stratejilere yeni bir bakış açısı sağlayabilir. 

Anahtar Kelimeler

Adrenal bez , HMGB1 , inflamasyon , obezite , stereoloji.

Investigation of the Relationship Between HMGB1 and Obesity in the Adrenal Gland

Öz

Aim: The interaction between obesity and increased production of pro-inflammatory cytokines results the existence of inflammation HMGB1 secreted from the adrenal gland can play a role in inflammation pathways. The aim of this study is to explain the link between HMGB1 and obesity in the adrenal gland.
Material and Methods: In this study; eighteen female Wistar Albino rats were divided into two groups: untreated control group (n=8) and obese group (n=10). The rats in obese group were fed with high fat diet for ten weeks. Morphometric parameters of adrenal gland were assessed by using stereological techniques. The expression of high mobility group box protein 1 (HMGB1) in adrenal gland was evaluated.
Results: At the end of the analyses; mean volumes of zona fasciculate, zona reticularis, and medulla were significantly increased in obese group. Also, the number of HMGB1 stained cells was significantly increased in the obese group in comparison to control group.
Conclusion: The results suggest that obesity may be one of the reasons of inflammation and hypertrophy in the adrenal gland. HMGB1 may provide a novel perspective into the anti-inflammatory therapeutic strategies in obese patients.

Anahtar Kelimeler

Adrenal gland , HMGB1 , inflammation , obesity , stereology

Kaynakça

• 1. WHO. Obesity and overweight. Available from: (http://www.who.int/mediacentre/fact- sheets/fs311/en/) Accessed 10 Dec 2019
• 2. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology 2007;132: 2169-2180.
• 3. Deng T, Lyon CJ, Bergin S, Caligiuri MA, Hsueh WA. Obesity, Inflammation, and Cancer. Annu Rev Pathol 2016; 11: 421-449.
• 4. Mraz M, Haluzik M. The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol 2014; 222: R113-127.
• 5. Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 2008; 9: 367-377.
• 6. Mathieu P, Lemieux I, Despres JP. Obesity, inflammation, and cardiovascular risk. Clin Pharmacol Ther 2010; 87: 407-416.
• 7. Rocha VZ, Libby P. Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol 2009; 6: 399-409.
• 8. Aouadi M, Tencerova M, Vangala P, Yawe JC, Nicoloro SM, Amano SU, Cohen JL, Czech MP. Gene silencing in adipose tissue macrophages regulates whole-body metabolism in obese mice. Proc Natl Acad Sci U S A 2013; 110: 8278-8283.
• 9. Fernandez-Sanchez A, Madrigal-Santillan E, Bautista M, Esquivel-Soto J, Morales-Gonzalez A, Esquivel-Chirino C, Durante-Montiel I, Sánchez-Rivera G, Valadez-Vega C, Morales-González JA. Inflammation, Oxidative Stress, and Obesity. International Journal of Molecular Sciences 2011; 12: 3117-3132.
• 10. Hummasti S, Hotamisligil GS. Endoplasmic reticulum stress and inflammation in obesity and diabetes. Circ Res 2010; 107: 579-591.
• 11. Neels JG, Olefsky JM. Inflamed fat: what starts the fire? J Clin Invest 2006;116: 33-35.
• 12. Becatti M. Oxidative stress and high-mobility group box 1 (HMGB1) protein release in vitiligo. Br J Dermatol 2017;176: 1436-1437.
• 13. Kang R, Livesey KM, Zeh HJ, Lotze MT, Tang DL. HMGB1 as an autophagy sensor in oxidative stress. Autophagy 2011; 7: 904-906.
• 14. Tang DL, Kang R, Livesey KM, Cheh CW, Farkas A, Loughran P, Hoppe G, Bianchi ME, Tracey KJ, Zeh HJ 3rd, Lotze MT. Endogenous HMGB1 regulates autophagy. Journal of Cell Biology 2010; 190: 881-892.
• 15. Muller S, Scaffidi P, Degryse B, Bonaldi T, Ronfani L, Agresti A, Beltrame M, Bianchi ME. The double life of HMGB1 chromatin protein: architectural factor and extracellular signal. Embo Journal 2001; 20: 4337-4340.
• 16. Yang H, Tracey KJ. High mobility group box 1 (HMGB1). Crit Care Med 2005; 33: S472-474.
• 17. Zhang J, Zhang L, Zhang S, Yu Q, Xiong F, Huang K, Wang CY, Yang P. HMGB1, an innate alarmin, plays a critical role in chronic inflammation of adipose tissue in obesity. Mol Cell Endocrinol 2017; 454: 103-111.
• 18. Boutens L, Stienstra R. Adipose tissue macrophages: going off track during obesity. Diabetologia 2016; 59: 879-894.
• 19. Gunasekaran MK, Viranaicken W, Girard AC, Festy F, Cesari M, Roche R, Hoareau L.Inflammation triggers high mobility group box 1 (HMGB1) secretion in adipose tissue, a potential link to obesity. Cytokine 2013; 64: 103-111.
• 20. Pasquali R, Vicennati V, Gambineri A. Adrenal and gonadal function in obesity. Journal of Endocrinological Investigation 2002; 25: 893-898.
• 21. Swierczynska MM, Mateska I, Peitzsch M, Bornstein SR, Chavakis T, Eisenhofer G, et al. Changes in morphology and function of adrenal cortex in mice fed a high-fat diet. Int J Obes (Lond) 2015; 39: 321-330.
• 22. Ilmakunnas M, Tukiainen EM, Rouhiainen A, Rauvala H, Arola J, Nordin A, Mäkisalo H, Höckerstedt K, Isoniemi H.High mobility group box 1 protein as a marker of hepatocellular injury in human liver transplantation. Liver Transpl 2008; 14: 1517-1525.
• 23. Altunkaynak BZ, Altunkaynak E, Unal D, Unal B. A novel application for the cavalieri principle: a stereological and methodological study. Eurasian J Med 2009; 41: 99-101.
• 24. Altunkaynak BZ, Onger ME Altunkaynak E, Ayranci E, Canan S. A brief introduction to stereology and sampling strategies: basic concepts of stereology NeuroQuantology 2012; 10: 31.
• 25. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003; 348: 1625-1638.
• 26. Patel C, Ghanim H, Ravishankar S, Sia CL, Viswanathan P, Mohanty P, et al. Prolonged reactive oxygen species generation and nuclear factor-kappaB activation after a high-fat, high-carbohydrate meal in the obese. J Clin Endocrinol Metab 2007; 92: 4476-4479.
• 27. Zhang S, Zhong J, Yang P, Gong F, Wang CY. HMGB1, an innate alarmin, in the pathogenesis of type 1 diabetes. Int J Clin Exp Pathol 2009; 3: 24-38.
• 28. Cetin D, Lessig BA, Nasr E. Comprehensive Evaluation for Obesity: Beyond Body Mass Index. J Am Osteopath Assoc 2016; 116(6): 376-382.
• 29. Medjerab M, Abdelali M, Khalkhal A, Semiane N, Hammadi S, Mallek A, Bellahrache Z, Agoun H, Dahmani Y. Adrenal cortex disorders in a new model of obesity, Gerbillus gerbillus, exposed to a high carbohydrate diet, Comptes Rendus Biologies 2019; 342: 35-44.
• 30. Block G, Dietrich M, Norkus EP, Morrow JD, Hudes M, Caan B, Packer L. Factors associated with oxidative stress in human populations. Am J Epidemiol 2002; 156: 274-285.
• 31. Cetin D, Lessig BA, Nasr E. Comprehensive Evaluation for Obesity: Beyond Body Mass Index. J Am Osteopath Assoc 2016; 116: 376-382
• 32. Esposito K, Ciotola M, Schisano B, Misso L, Giannetti G, Ceriello A, et al. Oxidative stress in the metabolic syndrome. J Endocrinol Invest 2006; 29: 791-795.
• 33. Pihl E, Zilmer K, Kullisaar T, Kairane C, Magi A, Zilmer M. Atherogenic inflammatory and oxidative stress markers in relation to overweight values in male former athletes. Int J Obes (Lond) 2006; 30: 141-146.
• 34. Savini I, Gasperi V, Catani MV. Oxidative Stress and Obesity. In: Ahmad S., Imam S. (eds) Obesity. Springer, Cham. 2016 https://doi.org/10.1007/978-3-319-19821-7_6
• 35. Gaman M, Epingeac ME, Gad M, Diaconu CC, Gaman AM. Oxidative Stress Levels Are Increased In Obesity And Obesity-Related Complications. Journal of Hypertension 2019; 37: e206-e207, doi: 10.1097/01.hjh.0000572664.53292.92
• s a critical role in chronic inflammation of adipose tissue in obesity. Mol Cell Endocrinol. 2017; 454:103-111, PMID: 28619625.
• 37. Abu El-Asrar AM, Alam K, Garcia-Ramirez M, Ahmad A, Siddiquei MM. Mohammad G, et al., Association of HMGB1 with oxidative stress markers and regulators in PDR. Molecular vision 2017; 23: 853–871,
• 38.Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol 2015; 15: 104-116.
• 39. White PC. Steroid 11 beta-hydroxylase deficiency and related disorders. Endocrinol Metab Clin North Am 2001, 30: 61-79.
• 40. Chen L, Zhu H, Su S, Harshfield G, Sullivan J, Webb C, Blumenthal JA, Wang X, Huang Y, Treiber FA, Kapuku G, Li W, Dong Y. High-mobility group box-1 is associated with obesity, inflammation, and subclinical cardiovascular risk among young adults: A longitudinal cohort study. Arterioscler Thromb Vasc Biol. 2020; 40: 2776-2784.