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The influence of gastric bypass surgery on the concentration of high mobility group box 1, nuclear factor erythroid 2–related factor 2 and the genes expression of high mobility group box 1, nuclear factor erythroid2–related factor 2, interleukin 6, and tumor necrosis factor-alpha in the peripheral blood mononuclear cells of patients with morbid obesity

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Abstract

Background and objectives

Obesity is known as a disease with a chronic low-grade state of inflammation and high levels of oxidative stress. Given the challenges and consequences caused by obesity, obesity therapy is an essential subject to address. For sustainable weight loss, gastric bypass surgery is the most successful and essential option.

Methods

This prospective cohort study was performed on 35 patients aged (18–54) with morbid obesity (BMI: 42.06 kg/m2). Volunteers blood was taken, and peripheral blood mononuclear cells (PBMCs) were isolated, high mobility group box 1(HMGB1), nuclear factor erythroid2–related factor 2(Nrf2), Interleukin 6(IL-6), tumor necrosis factor-alpha (TNF-α), and biochemical factors were determined one day before and 4 months after surgery.

Results

Four months following surgery, the BMI, hip and waist circumferences, and waist-to-hip ratio (WHR) all decreased significantly. The lipid profile and antioxidant power were dramatically enhanced after surgery. IL-6 and TNF-α expression in PBMC patients showed a significant decrease after surgery. HMGB1 and Nrf2 expression in PBMC of postoperative patients decreased compared to before surgery, and HMGB1, and Nrf2 protein levels also decreased after surgery.

Conclusion

Weight loss indicated the significant function of adipose tissue in the induction of oxidative stress and inflammatory factors. Gastric bypass reduced the inflammation conditions and improved the metabolic status and living situations in the patients with morbid obesity.

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References

  1. Organization WH (2018) WHO Media Centre. Obesity and overweight: fact sheet (No. 311)

  2. Samad F, Ruf W (2013) Inflammation, obesity, and thrombosis. Blood 122(20):3415–3422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Andersson U, Tracey KJ (2004) HMGB1 as a mediator of necrosis-induced inflammation and a therapeutic target in arthritis. Rheum Dis Clin 30(3):627–637

    Article  Google Scholar 

  4. Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418(6894):191–195

    Article  CAS  PubMed  Google Scholar 

  5. Magna M, Pisetsky DS (2016) The alarmin properties of DNA and DNA-associated nuclear proteins. Clin Ther 38(5):1029–1041

    Article  CAS  PubMed  Google Scholar 

  6. Wagner M (2014) A dangerous duo in adipose tissue: high-mobility group box 1 protein and macrophages. Yale J Biol Med 87(2):127

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Gesta S, Tseng Y-H, Kahn CR (2007) Developmental origin of fat: tracking obesity to its source. Cell 131(2):242–256

    Article  CAS  PubMed  Google Scholar 

  8. Park JS, Svetkauskaite D, He Q, Kim J-Y, Strassheim D, Ishizaka A et al (2004) Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem 279(9):7370–7377

    Article  CAS  PubMed  Google Scholar 

  9. Vanacore D, Messina G, Lama S, Bitti G, Ambrosio P, Tenore G et al (2018) Effect of restriction vegan diet’s on muscle mass, oxidative status, and myocytes differentiation: a pilot study. J Cell Physiol 233(12):9345–9353

    Article  CAS  PubMed  Google Scholar 

  10. Vincent HK, Taylor AG (2006) Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans. Int J Obes 30(3):400–418

    Article  CAS  Google Scholar 

  11. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y et al (2017) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Investig 114(12):1752–1761

    Article  Google Scholar 

  12. More VR, Xu J, Shimpi PC, Belgrave C, Luyendyk JP, Yamamoto M et al (2013) Keap1 knockdown increases markers of metabolic syndrome after long-term high fat diet feeding. Free Radic Biol Med 61:85–94

    Article  CAS  PubMed  Google Scholar 

  13. de Haan JB (2011) Nrf2 activators as attractive therapeutics for diabetic nephropathy. Diabetes 60(11):2683–2684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Loh K, Deng H, Fukushima A, Cai X, Boivin B, Galic S et al (2009) Reactive oxygen species enhance insulin sensitivity. Cell Metab 10(4):260–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Taguchi K, Motohashi H, Yamamoto M (2011) Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution. Genes Cells 16(2):123–140

    Article  CAS  PubMed  Google Scholar 

  16. Shin S, Wakabayashi J, Yates MS, Wakabayashi N, Dolan PM, Aja S et al (2009) Role of Nrf2 in prevention of high-fat diet-induced obesity by synthetic triterpenoid CDDO-imidazolide. Eur J Pharmacol 620(1–3):138–144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Heneghan HM, Heinberg L, Windover A, Rogula T, Schauer PR (2012) Weighing the evidence for an association between obesity and suicide risk. Surg Obes Relat Dis 8(1):98–107

    Article  PubMed  Google Scholar 

  18. Wittgrove AC, Clark GW, Tremblay LJ (1994) Laparoscopic gastric bypass, Roux-en-Y: preliminary report of five cases. Obes Surg 4(4):353–357

    Article  CAS  PubMed  Google Scholar 

  19. Ingelfinger JR (2011) Bariatric surgery in adolescents. N Engl J Med 365(15):1365–1367

    Article  CAS  PubMed  Google Scholar 

  20. Farrell TM, Haggerty SP, Overby DW, Kohn GP, Richardson WS, Fanelli RD (2009) Clinical application of laparoscopic bariatric surgery: an evidence-based review. Surg Endosc 23(5):930–949

    Article  PubMed  Google Scholar 

  21. Valette M, Poitou C, Le Beyec J, Bouillot J-L, Clement K, Czernichow S (2012) Melanocortin-4 receptor mutations and polymorphisms do not affect weight loss after bariatric surgery. PLoS ONE 7(11):e48221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhou K, Wolski K, Malin SK, Aminian A, Schauer PR, Bhatt DL et al (2019) Impact of weight loss trajectory following randomization to bariatric surgery on long-term diabetes glycemic and cardiometabolic parameters. Endocr Pract 25(6):572–579

    Article  PubMed  Google Scholar 

  23. Organization WH (2016) World Health Organization obesity and overweight fact sheet

  24. Csige I, Ujvárosy D, Szabó Z, Lőrincz I, Paragh G, Harangi M et al (2018) The impact of obesity on the cardiovascular system. J Diabetes Res. https://doi.org/10.1155/2018/3407306

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pecht T, Haim Y, Bashan N, Shapiro H, Harman-Boehm I, Kirshtein B et al (2016) Circulating blood monocyte subclasses and lipid-laden adipose tissue macrophages in human obesity. PLoS ONE 11(7):e0159350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Choromańska B, Myśliwiec P, Łuba M, Wojskowicz P, Dadan J, Myśliwiec H et al (2020) A longitudinal study of the antioxidant barrier and oxidative stress in morbidly obese patients after bariatric surgery. Does the metabolic syndrome affect the redox homeostasis of obese people? J Clin Med 9(4):976

    Article  CAS  PubMed Central  Google Scholar 

  27. Rai MF, Sandell L (2011) Inflammatory mediators: tracing links between obesity and osteoarthritis. Crit Rev Eukaryot Gene Expr 21(2):131

    Article  CAS  PubMed  Google Scholar 

  28. Vincent HK, Bourguignon CM, Taylor AG (2010) Relationship of the dietary phytochemical index to weight gain, oxidative stress and inflammation in overweight young adults. J Hum Nutr Diet 23(1):20–29

    Article  CAS  PubMed  Google Scholar 

  29. Boccellino M, Camussi G, Giovane A, Ferro L, Calderaro V, Balestrieri C et al (2005) Platelet-activating factor regulates cadherin-catenin adhesion system expression and β-catenin phosphorylation during Kaposi’s sarcoma cell motility. Am J Pathol 166(5):1515–1522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Boccellino M, Giuberti G, Quagliuolo L, Marra M, D’Alessandro A, Fujita H et al (2004) Apoptosis induced by interferon-α and antagonized by EGF is regulated by caspase-3-mediated cleavage of gelsolin in human epidermoid cancer cells. J Cell Physiol 201(1):71–83

    Article  CAS  PubMed  Google Scholar 

  31. Karaouzene N, Merzouk H, Aribi M, Merzouk S, Berrouiguet AY, Tessier C et al (2011) Effects of the association of aging and obesity on lipids, lipoproteins and oxidative stress biomarkers: a comparison of older with young men. Nutr Metab Cardiovasc Dis 21(10):792–799

    Article  CAS  PubMed  Google Scholar 

  32. Kuo F-C, Huang Y-H, Lin F-H, Hung Y-J, Hsieh C-H, Lu C-H et al (2017) Circulating soluble IL-6 receptor concentration and visceral adipocyte size are related to insulin resistance in Taiwanese adults with morbid obesity. Metab Syndr Relat Disord 15(4):187–193

    Article  CAS  PubMed  Google Scholar 

  33. Pourrajab F, Sharifi M, Hekmatimoghaddam S, Khanaghaei M, Rahaie M (2016) Elevated levels of miR-499 protect ischemic myocardium against uric acid in patients undergoing off-pump CABG. Cor Vasa 58(6):e600–e608

    Article  Google Scholar 

  34. Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38(12):1103–1111

    Article  CAS  PubMed  Google Scholar 

  35. Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ (2009) HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol 28:367–388

    Article  CAS  Google Scholar 

  36. Lee EB (2011) Obesity, leptin, and Alzheimer’s disease. Ann N Y Acad Sci 1243:15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tanaka Y, Aleksunes LM, Yeager RL, Gyamfi MA, Esterly N, Guo GL et al (2008) NF-E2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet. J Pharmacol Exp Ther 325(2):655–664

    Article  CAS  PubMed  Google Scholar 

  38. Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M et al (2009) Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci USA 106(21):8665–8670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Vilarrasa N, Vendrell J, Sánchez-Santos R, Broch M, Megia A, Masdevall C et al (2007) Effect of weight loss induced by gastric bypass on proinflammatory interleukin-18, soluble tumour necrosis factor-α receptors, C-reactive protein and adiponectin in morbidly obese patients. Clin Endocrinol 67(5):679–686

    Article  CAS  Google Scholar 

  40. Arrigo T, Chirico V, Salpietro V, Munafo C, Ferrau V, Gitto E et al (2013) High-mobility group protein B1: a new biomarker of metabolic syndrome in obese children. Eur J Endocrinol 168(4):631–638

    Article  CAS  PubMed  Google Scholar 

  41. Giacobbe A, Grasso R, Imbesi G, Salpietro C, Grasso L, Lagana A et al (2015) High mobility group protein B1: a new biomarker of obesity in pregnant women? Gynecol Endocrinol 31(2):113–115

    Article  CAS  PubMed  Google Scholar 

  42. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Investig 112(12):1796–1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Eichelmann F, Schwingshackl L, Fedirko V, Aleksandrova K (2016) Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials. Obes Rev 17(11):1067–1079

    Article  CAS  PubMed  Google Scholar 

  44. Viana EC, Araujo-Dasilio KL, Miguel GPS, Bressan J, Lemos EM, Moyses MR et al (2013) Gastric bypass and sleeve gastrectomy: the same impact on IL-6 and TNF-α. Prospective clinical trial. Obes Surg 23(8):1252–1261

    Article  PubMed  Google Scholar 

  45. Nativel B, Marimoutou M, Thon-Hon VG, Gunasekaran MK, Andries J, Stanislas G et al (2013) Soluble HMGB1 is a novel adipokine stimulating IL-6 secretion through RAGE receptor in SW872 preadipocyte cell line: contribution to chronic inflammation in fat tissue. PLoS ONE 8(9):e76039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jin C, Henao-Mejia J, Flavell RA (2013) Innate immune receptors: key regulators of metabolic disease progression. Cell Metab 17(6):873–882

    Article  CAS  PubMed  Google Scholar 

  47. Montes V, Subramanian S, Goodspeed L, Wang S, Omer M, Bobik A et al (2015) Anti-HMGB1 antibody reduces weight gain in mice fed a high-fat diet. Nutr Diabetes 5(6):e161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Borbély YM, Osterwalder A, Kröll D, Nett PC, Inglin RA (2017) Diarrhea after bariatric procedures: diagnosis and therapy. World J Gastroenterol 23(26):4689

    Article  PubMed  PubMed Central  Google Scholar 

  49. Guman M, van Olst N, Yaman Z, Voermans R, de Brauw L, Nieuwdorp M et al (2021) Pancreatic exocrine insufficiency after bariatric surgery. Surg Obes Relat Dis. https://doi.org/10.1016/j.soard.2021.12.017

    Article  PubMed  Google Scholar 

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Acknowledgements

This report was taken from a PhD thesis at Hamadan University of Medical Sciences, Iran. The research was funded by Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences, Iran (No. 9811158686).

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Correspondence to Roghayeh Abbasalipourkabir.

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The study was approved by the Ethics Committee of the Hamadan University of Medical Sciences (IR.UMSHA.REC.1398.910).

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Khanaghaei, M., Ziamajidi, N., Poorolajal, J. et al. The influence of gastric bypass surgery on the concentration of high mobility group box 1, nuclear factor erythroid 2–related factor 2 and the genes expression of high mobility group box 1, nuclear factor erythroid2–related factor 2, interleukin 6, and tumor necrosis factor-alpha in the peripheral blood mononuclear cells of patients with morbid obesity. Mol Biol Rep 49, 3745–3755 (2022). https://doi.org/10.1007/s11033-022-07214-6

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