Skip to main content Skip to main navigation menu Skip to site footer

High levels of interleukin-6 and triglycerides and low levels of soluble leptin receptors as risk factors for leptin resistance in obese adolescents

Abstract

Introduction: Obesity is a nutritional disorder that can affect all ages, including teenagers. Obesity can affect gut microbiota and cause increased intestinal permeability. This process leads to interleukin-6 and TNF-α production which can increase leptin levels. The soluble leptin receptor (sLR) is a leptin receptor in the plasma that transports leptin to the hypothalamus. Low sLR numbers are associated with high leptin levels in obesity. Obesity in hyperleptinemia conditions indicates leptin resistance (defects in leptin receptors) which causes hyperphagia and reduces energy expenditure. This study was conducted to prove high TG and IL-6 serum levels and low sLR levels in obese adolescents who have a higher risk of developing leptin resistance than normal adolescents.

Methods: This research is a case-control study. The subjects underwent an assessment including food recall, anthropometric status, and lipid profile. The food recall assessment was obtained by means of a questionnaire given to parents. Blood sampling and laboratory examination are carried out by the Prodia® Clinical Laboratory. Data analysis was performed by computer, using the Independent t-test, Mann-Whitney test. Chi-Square test, and analysis of the ROC curve.

Results: ROC curve analysis obtained the optimal cut points for TG and IL-6 levels, respectively 101.5 mg/dL (sensitivity 82.1%, specificity 89.7%) and 11.95 pg/mL (sensitivity 84.6%, specificity of 80%), with area under the curve (AUC) values of 0.96 and 0.89, respectively. ROC curve analysis obtained the optimal cut point for sLR levels of 19.3 ng/mL (sensitivity 64.1%, specificity 71.8%) with an AUC value of 0.77. Multivariate analysis using logistic regression found a significant relationship between TG and IL-6 levels on the incidence of hyperleptinemia.

Conclusion: This study reinforces the theory of chronic low-grade inflammation and proved that inflammation and high TG levels play a role in hyperleptinemia in obese adolescents.

References

  1. Rahmouni K, Correia MLG, Haynes WG, Mark AL. Obesity-Associated Hypertension. Hypertension. 2005;45(1):9–14. Available from: http://dx.doi.org/10.1161/01.hyp.0000151325.83008.b4
  2. De Onis M. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatrica, International Journal of Paediatrics. 2006;95(SUPPL. 450):76–85.
  3. Dwipayana IMP, Gotera W, Suastika K, Yasa IWPS, Budhiarta AAG, Saraswati MR, et al. Association between insulin, glucagon, high sensitive c-reactive protein, insulin resistance with visceral adipose tissue-derived serine protease inhibitor (VASPIN) in obese population. Bali Medical Journal. 2022;11(3):1717–20.
  4. Kementerian Kesehatan RI. Laporan Riskesdas 2018. Laporan Nasional Riskesdas 2018. 2018;53(9):154–65.
  5. Kansra AR, Lakkunarajah S, Jay MS. Childhood and Adolescent Obesity: A Review. Vol. 8, Frontiers in Pediatrics. Frontiers Media S.A.; 2021.
  6. Cozzolino SMF, Marreiro DDN, Fisberg M. Zinc Nutritional Status in Obese Children and Adolescents. Biol Trace Elem Res. 2002;86(2):107–22. Available from: http://dx.doi.org/10.1385/bter:86:2:107
  7. Nakamura YK, Omaye ST. Metabolic diseases and pro- and prebiotics: Mechanistic insights. Nutr Metab (Lond). 2012;9(1):60. Available from: https://pubmed.ncbi.nlm.nih.gov/22713169
  8. Hakansson A, Molin G. Gut microbiota and inflammation. Nutrients. 2011/06/03. 2011;3(6):637–82. Available from: https://pubmed.ncbi.nlm.nih.gov/22254115
  9. Ley RE. Obesity and the human microbiome. Curr Opin Gastroenterol. 2010;26(1):5–11. Available from: http://dx.doi.org/10.1097/mog.0b013e328333d751
  10. Gulo CIH, Puruhito, Novida H. The effectiveness of topical hyaluronic acid on decreasing Interleukin-6 and acceleration of wound healing (Push Score) in Wagner II-III diabetic foot ulcer in Dr. Soetomo Hospital Surabaya. Bali Medical Journal. 2022;11(3):1049–53.
  11. Abdullah A, Jamil KF, Lindarto D, Salwani D, Muhsin M, Khairi AB, et al. Declining in estimated glomerular filtration rate of chronic kidney disease patients after Ramadan fasting is independent of interleukin-6 serum level. Bali Medical Journal. 2023;12(1):94–8.
  12. Sader S, Nian M, Liu P. Leptin. Circulation. 2003;108(6):644–6. Available from: http://dx.doi.org/10.1161/01.cir.0000081427.01306.7d
  13. Fried SK, Ricci MR, Russell CD, Laferrère B. Regulation of Leptin Production in Humans. J Nutr. 2000;130(12):3127S-3131S. Available from: http://dx.doi.org/10.1093/jn/130.12.3127s
  14. Ogier V, Ziegler O, Méjean L, Nicolas JP, Stricker-Krongrad A. Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans. Int J Obes. 2002;26(4):496–503. Available from: http://dx.doi.org/10.1038/sj.ijo.0801951
  15. Banks WA, Coon AB, Robinson SM, Moinuddin A, Shultz JM, Nakaoke R, et al. Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier. Diabetes. 2004;53(5):1253–60. Available from: http://dx.doi.org/10.2337/diabetes.53.5.1253
  16. Münzberg H, Björnholm M, Bates SH, Myers MG. Leptin receptor action and mechanisms of leptin resistance. Cellular and Molecular Life Sciences. 2005;62(6). Available from: http://dx.doi.org/10.1007/s00018-004-4432-1
  17. World Health Organization. Obesity : preventing and managing the global epidemic : report of a WHO consultation. World Health Organization; 2000. 253 p.
  18. Kuczmarski RJ, National Center for Health Statistics (U.S.), National Health and Nutrition Examination Survey (U.S.). 2000 CDC growth charts for the United States : methods and development. Dept. of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics; 2002. 190 p.
  19. Cani P, Delzenne N. The Role of the Gut Microbiota in Energy Metabolism and Metabolic Disease. Curr Pharm Des. 2009;15(13):1546–58. Available from: http://dx.doi.org/10.2174/138161209788168164
  20. Jung MK, Yoo E-G. Hypertriglyceridemia in Obese Children and Adolescents. J Obes Metab Syndr. 2018;27(3):143–9. Available from: https://pubmed.ncbi.nlm.nih.gov/31089556
  21. Carter S, Caron A, Richard D, Picard F. Role of leptin resistance in the development of obesity in older patients. Clin Interv Aging. 2013/07/04. 2013;8:829–44. Available from: https://pubmed.ncbi.nlm.nih.gov/23869170
  22. Moreira APB, Texeira TFS, Ferreira AB, do Carmo Gouveia Peluzio M, de Cássia Gonçalves Alfenas R. Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. British Journal of Nutrition. 2012;108(5):801–9. Available from: http://dx.doi.org/10.1017/s0007114512001213
  23. da Silva ST, dos Santos CA, Bressan J. Microbiota intestinal; relevancia para la obesidad y la modulación de los prebióticos y probióticos. Vol. 28, Nutricion Hospitalaria. 2013. p. 1039–48.
  24. Rajendran K, Devarajan N, Ganesan M, Ragunathan M. Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population. Thromb J. 2012;10(1):13. Available from: https://pubmed.ncbi.nlm.nih.gov/22891684
  25. Nyangasa MA, Buck C, Kelm S, Sheikh MA, Günther K, Hebestreit A. The association between leptin and inflammatory markers with obesity indices in Zanzibari children, adolescents, and adults. Obes Sci Pract. 2020;7(1):71–81. Available from: https://pubmed.ncbi.nlm.nih.gov/33680494
  26. Wärnberg J, Moreno LA, Mesana MI, Marcos A. Inflammatory mediators in overweight and obese spanish adolescents. The avena study. Int J Obes. 2004;28:S59–63.
  27. Yang R, Barouch LA. Leptin Signaling and Obesity. Circ Res. 2007;101(6):545–59. Available from: http://dx.doi.org/10.1161/circresaha.107.156596
  28. Reinehr T, De Sousa G, Roth CL. Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight. Clin Endocrinol (Oxf). 2008;68(2):304–10.
  29. Sinha MK, Opentanova I, Ohannesian JP, Kolaczynski JW, Heiman ML, Hale J, et al. Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest. 1996;98(6):1277–82. Available from: https://pubmed.ncbi.nlm.nih.gov/8823291
  30. Cinaz P, Bideci A, Çamurdan MO, Gilven A, Gönen S. Leptin and Soluble Leptin Receptor Levels in Obese Children in Fasting and Satiety States. Journal of Pediatric Endocrinology and Metabolism. 2005;18(3). Available from: http://dx.doi.org/10.1515/jpem.2005.18.3.303
  31. Considine R V, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans. New England Journal of Medicine. 1996;334(5):292–5. Available from: http://dx.doi.org/10.1056/nejm199602013340503
  32. Hemmingsson E, Ekelund U. Is the association between physical activity and body mass index obesity dependent? Int J Obes. 2006;31(4):663–8. Available from: http://dx.doi.org/10.1038/sj.ijo.0803458
  33. Fukuda S, Morimoto K. Lifestyle, stress and cortisol response: Review II : Lifestyle. Environ Health Prev Med. 2001;6(1):15–21. Available from: https://pubmed.ncbi.nlm.nih.gov/21432232

How to Cite

Pinatih, K. J. P., Karyana, I. P. G. ., Nesa, N. N. M. ., Apsari, N. L. S. ., & Wihandani, D. M. . (2023). High levels of interleukin-6 and triglycerides and low levels of soluble leptin receptors as risk factors for leptin resistance in obese adolescents. Bali Medical Journal, 12(2), 1204–1210. https://doi.org/10.15562/bmj.v12i2.4371

HTML
30

Total
16

Share

Search Panel

Komang Januartha Putra Pinatih
Google Scholar
Pubmed
BMJ Journal


I Putu Gede Karyana
Google Scholar
Pubmed
BMJ Journal


Ni Nyoman Metriani Nesa
Google Scholar
Pubmed
BMJ Journal


Ni Luh Sri Apsari
Google Scholar
Pubmed
BMJ Journal


Desak Made Wihandani
Google Scholar
Pubmed
BMJ Journal