Preoperative Chemerin Level Is Predictive of Inflammatory Status 1 Year After Bariatric Surgery

Abstract

Background

Obesity is associated with chronic low-grade inflammation, which has been linked to increased morbidity. However, inflammation variably and unpredictably improves after bariatric surgery. This study aimed at (1) evaluating the relationship between amplitude of weight loss and variation of inflammatory parameters after bariatric surgery, and (2) identifying, among clinical and biological baseline parameters, predictive factors of variation in inflammatory parameters.

Methods

In a prospective cohort of patients who underwent bariatric surgery, serum concentrations of interleukin (IL)-6, IL-10, resistin, leptin, adiponectin chemerin, and C-reactive protein (CRP) were measured preoperatively and 1 year after surgery, and routine clinical and biochemical parameters were retrieved. Univariate and multivariate analyses (partial least square method) were performed to assess how parameters were associated with weight loss and to predict improvement of inflammatory parameters.

Results

Eighty-seven patients were included (mean weight ± SD 136.3 ± 3.2 kg, 35 gastric bypasses, 52 sleeve gastrectomies). In parallel with weight loss (39.5 ± 13.8 kg), pro-inflammatory markers (IL-6, CRP, leptin, resistin) significantly decreased, and anti-inflammatory markers (IL-10, adiponectin) increased. Multivariate analysis revealed a significant association between weight loss and improvement in inflammatory parameters. Among all the clinical and biological preoperative parameters, baseline chemerin level was the only parameter that was significantly associated with global improvement of the inflammatory status after surgery.

Conclusion

The amplitude of weight loss 1 year after bariatric surgery was strongly correlated with improvement of inflammatory profile, which could be predicted by baseline plasma level of chemerin. This suggests a key role of chemerin in obesity-driven inflammation, and a potential use as a biomarker.

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References

  1. 1.

    Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. Elsevier. 2014;384(9945):766–81

  2. 2.

    Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet Elsevier. 2005;365(9468):1415–28.

    PubMed  CAS  Google Scholar 

  3. 3.

    Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–7.

    CAS  Google Scholar 

  4. 4.

    de Heredia FP, Gómez-Martínez S, Marcos A. Obesity, inflammation and the immune system. Proc Nutr Soc Cambridge University Press. 2012;71(02):332–8.

    PubMed  Google Scholar 

  5. 5.

    Rodríguez-Hernández H, Simental-Mendía LE, Rodríguez-Ramírez G, et al. Obesity and Inflammation: epidemiology, risk factors, and markers of inflammation. Int J Endocrinol. Hindawi Publishing Corporation. 2013;2013(10):1–11.

    Google Scholar 

  6. 6.

    Visser M, Bouter LM, McQuillan GM, et al. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999;282(22):2131–5.

    PubMed  CAS  Google Scholar 

  7. 7.

    Park H, Park Y, Yu R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-a and IL-6. Diabetes Res Clin Pract. 2005;69:1–7.

    Google Scholar 

  8. 8.

    Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. Nature Publishing Group. 2014;14(7):463–77.

    PubMed  CAS  Google Scholar 

  9. 9.

    Gisterå A, Hansson GK. The immunology of atherosclerosis. Nat Rev Nephrol. 2017;13(6):368–80.

    PubMed  Google Scholar 

  10. 10.

    Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. Nature Publishing Group. 2008;454(7203):436–44.

    PubMed  PubMed Central  CAS  Google Scholar 

  11. 11.

    Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2015;16(1):22–34.

    Google Scholar 

  12. 12.

    Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69(Suppl 1):S4–9.

    PubMed  Google Scholar 

  13. 13.

    Lackey DE, Olefsky JM. Regulation of metabolism by the innate immune system. Nat Rev Endocrinol. 2016;12(1):15–28.

    PubMed  CAS  Google Scholar 

  14. 14.

    Brestoff JR, Artis D. Immune regulation of metabolic homeostasis in health and disease. Cell. Elsevier. 2015;161(1):146–60.

    PubMed  PubMed Central  CAS  Google Scholar 

  15. 15.

    Ouchi N, Parker JL, Lugus JJ, et al. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85–97.

    PubMed  PubMed Central  CAS  Google Scholar 

  16. 16.

    Ohashi K, Ouchi N, Matsuzawa Y. Anti-inflammatory and anti-atherogenic properties of adiponectin. Biochimie. 2012;94(10):2137–42.

    PubMed  CAS  Google Scholar 

  17. 17.

    Cao H. Adipocytokines in obesity and metabolic disease. J Endocrinol. BioScientifica. 2014;220(2):T47–59.

    PubMed  PubMed Central  CAS  Google Scholar 

  18. 18.

    Ernst MC, Sinal CJ. Chemerin: at the crossroads of inflammation and obesity. Trends Endocrinol Metab. Elsevier Ltd. 2010;21(11):660–7.

    PubMed  CAS  Google Scholar 

  19. 19.

    Helfer G, Wu Q-F. Chemerin: a multifaceted adipokine involved in metabolic disorders. J Endocrinol. Bioscientifica Ltd. 2018;238(2):R79–94.

    PubMed  PubMed Central  CAS  Google Scholar 

  20. 20.

    Rourke JL, Dranse HJ, Sinal CJ. Towards an integrative approach to understanding the role of chemerin in human health and disease. Obes Rev. 2012;14(3):245–62.

    PubMed  Google Scholar 

  21. 21.

    Chang S-S, Eisenberg D, Zhao L, et al. Chemerin activation in human obesity. Obesity. 2016;24(7):1522–9.

    PubMed  CAS  Google Scholar 

  22. 22.

    Li Y, Shi B, Li S. Association between serum chemerin concentrations and clinical indices in obesity or metabolic syndrome: a meta-analysis. Villa E, editor. PLoS ONE. Public Library of Science; 2014;9(12):e113915–14.

  23. 23.

    Colquitt JL, Pickett K, Loveman E, et al. Surgery for weight loss in adults. In: Colquitt JL, editor. Cochrane Database Syst Rev, vol. 8. Chichester: John Wiley & Sons, Ltd; 2014. p. CD003641.

    Google Scholar 

  24. 24.

    Picot J, Jones J, Colquitt JL, et al. The clinical effectiveness and cost-effectiveness of bariatric (weight loss) surgery for obesity: a systematic review and economic evaluation. Health Technol Assess. 2009;13(41):1. –190–215–357–iii–iv

    PubMed  CAS  Google Scholar 

  25. 25.

    Frikke-Schmidt H, O’Rourke RW, Lumeng CN, et al. Does bariatric surgery improve adipose tissue function? Obes Rev. 2016;17(9):795–809

  26. 26.

    Goktas Z, Moustaid-Moussa N, Shen C-L, et al. Effects of bariatric surgery on adipokine-induced inflammation and insulin resistance. Front Endocrinol. Frontiers. 2013;4:69.

    Google Scholar 

  27. 27.

    Sauerland S, Angrisani L, Belachew M, et al. Obesity surgery: evidence-based guidelines of the European Association for Endoscopic Surgery (EAES). Surgical endoscopy. 2005;19(2):200–21

  28. 28.

    Laville M, Romon M, Chavrier G, et al. Recommendations regarding obesity surgery. Obes Surg. Springer-Verlag. 2005;15(10):1476–80.

    PubMed  CAS  Google Scholar 

  29. 29.

    Haute Autorité de Santé. Obésité: prise en charge chirurgicale de l’adulte [Internet]. 2009. Available from: http://www.has-sante.fr

  30. 30.

    Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85(7):2402–10.

    PubMed  CAS  Google Scholar 

  31. 31.

    Iacobini C, Pugliese G, Fantauzzi CB, et al. Metabolically healthy versus metabolically unhealthy obesity. Metabolism Elsevier Inc. 2019;92(C):51–60.

    PubMed  CAS  Google Scholar 

  32. 32.

    Arismendi E, Rivas E, Agustí A, Ríos J, Barreiro E, Vidal J, et al. The systemic inflammome of severe obesity before and after bariatric surgery. Thatcher TH, editor. PLoS ONE. Public Library of Science; 2014;9(9):e107859.

  33. 33.

    Iannelli A, Anty R, Schneck AS, et al. Evolution of low-grade systemic inflammation, insulin resistance, anthropometrics, resting energy expenditure and metabolic syndrome after bariatric surgery: a comparative study between gastric bypass and sleeve gastrectomy. J Visc Surg. Elsevier Masson SAS. 2013;150(4):269–75.

    PubMed  CAS  Google Scholar 

  34. 34.

    Gumbau V, Bruna M, Canelles E, et al. A prospective study on inflammatory parameters in obese patients after sleeve gastrectomy. Obes Surg. Springer US. 2014;24(6):903–8.

    PubMed  Google Scholar 

  35. 35.

    Catalán V, Gómez-Ambrosi J, Rodríguez A, et al. Increased levels of chemerin and its receptor, chemokine-like receptor-1, in obesity are related to inflammation: tumor necrosis factor-α stimulates mRNA levels of chemerin in visceral adipocytes from obese patients. Surg Obes Relat Dis. Elsevier Inc. 2013;9(2):306–14.

    PubMed  Google Scholar 

  36. 36.

    Miller GD, Nicklas BJ, Fernandez A. Serial changes in inflammatory biomarkers after Roux-en-Y gastric bypass surgery. Surg Obes Relat Dis. Elsevier Inc. 2011;7(5):618–24.

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Netto BDM, Bettini SC, Clemente APG, et al. Roux-en-Y gastric bypass decreases pro-inflammatory and thrombotic biomarkers in individuals with extreme obesity. Obes Surg. 2014;25(6):1010–8.

    Google Scholar 

  38. 38.

    Dalmas E, Rouault C, Abdennour M, et al. Variations in circulating inflammatory factors are related to changes in calorie and carbohydrate intakes early in the course of surgery-induced weight reduction. Am J Clin Nutr. American Society for Nutrition. 2011;94(2):450–8.

    PubMed  CAS  Google Scholar 

  39. 39.

    Vilarrasa N, Vendrell J, Sánchez-Santos R, et al. 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. Blackwell Publishing Ltd. 2007;67(5):679–86.

    CAS  Google Scholar 

  40. 40.

    Morínigo R, Casamitjana R, Delgado S, et al. Insulin resistance, inflammation, and the metabolic syndrome following Roux-en-Y gastric bypass surgery in severely obese subjects. Diabetes Care. American Diabetes Association. 2007;30(7):1906–8.

    PubMed  Google Scholar 

  41. 41.

    Marantos G, Daskalakis M, Karkavitsas N, et al. Changes in metabolic profile and adipoinsular axis in morbidly obese premenopausal females treated with restrictive bariatric surgery. World J Surg. 2011;35(9):2022–30.

    PubMed  Google Scholar 

  42. 42.

    Ress C, Tschoner A, Engl J, et al. Effect of bariatric surgery on circulating chemerin levels. Eur J Clin Investig. Wiley/Blackwell (10.1111). 2010;40(3):277–80.

    CAS  Google Scholar 

  43. 43.

    Sell H, Divoux A, Poitou C, et al. Chemerin correlates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery. J Clin Endocrinol Metab. 2010;95(6):2892–6.

    PubMed  CAS  Google Scholar 

  44. 44.

    Terra X, Auguet T, Guiu-Jurado E, et al. Long-term changes in leptin, chemerin and ghrelin levels following different bariatric surgery procedures: Roux-en-Y gastric bypass and sleeve gastrectomy. Obes Surg. Springer US. 2013;23(11):1790–8.

    PubMed  Google Scholar 

  45. 45.

    Freitas WR, Oliveira LVF, Perez EA, et al. Systemic inflammation in severe obese patients undergoing surgery for obesity and weight-related diseases. Obes Surg Obesity Surgery. 2018;307(5):1–12.

    Google Scholar 

  46. 46.

    Debnath M, Agrawal S, Agrawal A, et al. Metaflammatory responses during obesity: pathomechanism and treatment. Obes Res Clin Pract. Asia Oceania Association for the Study of Obesity. 2015;10(2):1–11.

    Google Scholar 

  47. 47.

    Parlee SD, Ernst MC, Muruganandan S, et al. Serum chemerin levels vary with time of day and are modified by obesity and tumor necrosis factor-α. Endocrinology. 2010;151(6):2590–602.

    PubMed  CAS  Google Scholar 

  48. 48.

    Bondue B, Wittamer V, Parmentier M. Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism. Cytokine Growth Factor Rev. Elsevier Ltd. 2011;22(5-6):331–8.

    PubMed  CAS  Google Scholar 

  49. 49.

    Mattern A, Zellmann T, Beck-Sickinger AG. Processing, signaling, and physiological function of chemerin. IUBMB Life. 2014;66(1):19–26.

    PubMed  CAS  Google Scholar 

  50. 50.

    Chakaroun R, Raschpichler M, Klöting N, et al. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism. 2012;61(5):706–14.

    PubMed  CAS  Google Scholar 

  51. 51.

    Del Prete A, Salvi V, Sozzani S. Adipokines as potential biomarkers in rheumatoid arthritis. Mediat Inflamm. Hindawi. 2014;2014(4):425068–11.

    Google Scholar 

  52. 52.

    Bai F, Zheng W, Dong Y, et al. Serum levels of adipokines and cytokines in psoriasis patients: a systematic review and meta-analysis. Oncotarget. 2018;9(1):1266–78.

    PubMed  Google Scholar 

  53. 53.

    Buechler C. Chemerin, a novel player in inflammatory bowel disease. Cell Mol Immunol. Nature Publishing Group. 2014;11(4):315–6.

    PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgments

We would like to thank Véronique Théret, Carole Sauvestre, Patricia Cosson, Marie-Céline Bourgoin, and Dr. David Jacobi. Some of the figures were created using the vector image bank of Servier Medical Art (http://smart.servier.com/). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/ by/3.0/).

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Correspondence to Youenn Jouan.

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All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards All patients included in the study gave written consent for scientific and anonymous use of their data, and the study was approved by the institutional ethic committee.

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Electronic Supplementary Material

ESM 1

Volcano plot representation of association between weight loss and variation of inflammatory and metabolic parameters, before and after bariatric surgery. Univariate analysis was performed to highlight the most discriminant parameters associated with weight loss. Results are represented as a volcano plot built on fold-change values and the threshold of significance using the non-parametric Wilcoxon test after adjustment for multiple test. (Reviewer #3, Q#3) The most relevant parameters were characterized by FC> 1.2 or <0.8 and adjusted p<0.2. (difference between baseline and one-year levels, noted Δ). Parameters with adjusted p=0.2 and fold change (FC) >1.2 or < 0.8 were considered as significant and are showed on the graph: variation of insulinemia, QUICKI and LDLc. QUICKI: quantitative insulin sensitivity check index; LDLc: low density lipoprotein cholesterol. (PDF 220 kb)

ESM 2

Predicting improvement of inflammatory parameters after surgery using baseline clinical and biological parameters. (A): In univariate analysis, among the selected inflammatory cytokines and adipokines, only IL-6 and adiponectin variations revealed significant association with baseline parameters. Parameters with adjusted p=0.2 and fold change (FC) >1.2 or < 0,8 were considered as significant. Thus, IL-6 variation before and after surgery was significantly associated with baseline IL-6 level (adjusted p =0.002, FC=3.3), and baseline resistin level (p=0.007, FC=1.9). Adiponectin variation before and after surgery was significantly associated with baseline adiponectin level (p=0.036 and FC=0.81) and baseline lean mass (adjusted p=0.026, FC=0.78). Volcano plots were next built for representations of association between fold change of variation of IL-6 and adiponectin before and after surgery (difference between baseline and one-year levels, noted “Δ”) and baseline parameters. Significant associations are mentioned on the graphs. (B): Results of multivariate analysis using non-optimized partial least square technic to explore association between baseline clinical and biological parameters and variation of selected inflammatory parameters (Resistin, CRP, Adiponectin and IL-6) before and after surgery (noted Δ), defined as < or > to the median. The two important measures in PLS-DA are represented: the variable importance in projection (VIP) and the weighted sum of absolute regression coefficients (the colored boxes on the right indicate the relative concentrations of the corresponding variable in each group under study). CRP: C-reactive protein; HDLc: high density lipoprotein cholesterol; LDLc: low density lipoprotein cholesterol; TG: Triglyceride. (PDF 1192 kb)

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Jouan, Y., Blasco, H., Bongrani, A. et al. Preoperative Chemerin Level Is Predictive of Inflammatory Status 1 Year After Bariatric Surgery. OBES SURG 30, 3852–3861 (2020). https://doi.org/10.1007/s11695-020-04584-3

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Keywords

  • Low-grade inflammation
  • Chemerin
  • Adipokines
  • Cytokines