Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Leptin, adiponectin, interleukin-6 and tumor necrosis factor-α in obese adolescents

비만아에서의 leptin, adiponectin, interleukin-6, tumor necrosis factor-α에 대한 연구

  • Gil, Joo Hyun (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Lee, Jung Ah (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Kim, Ji Young (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Hong, Young Mi (Department of Pediatrics, School of Medicine, Ewha Womans University)
  • 길주현 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 이정아 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 김지영 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 홍영미 (이화여자대학교 의학전문대학원 소아과학교실)
  • Received : 2007.12.05
  • Accepted : 2008.03.27
  • Published : 2008.06.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose : Obesity is associated with insulin resistance. Insulin resistance and the presence of pro-inflammatory mediators are thought to cause a state of vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation. These chronic inflammatory responses, which are characterized by abnormal cytokine production, lead to activation of a pro-inflammatory signaling pathway. Leptin is an important mediator of inflammatory processes and immune-mediated diseases. The purpose of this study was to investigate the relationship between leptin and various cytokines associated with obesity in adolescents. Methods : Sixty-six obese adolescents (between 16-17 years of age, obesity index >130%) and 26 normal controls were included in this study. Obesity index and body mass index (BMI) were calculated. Serum lipid profile, AST and ALT were tested after 10 hours of fasting. Tumor necrosis factor alpha (TNF-${\alpha}$) and Interleukin-6 (IL-6) levels were measured by ELISA. Insulin, adiponectin, and leptin levels were estimated by radioimmunoassay. Results : Leptin was significantly higher in the obese adolescents compared to the control adolescents ($12.0{\pm}6.8ng/mL$ vs $6.3{\pm}1.0ng/mL$). TNF-${\alpha}$, IL-6, and insulin were significantly higher in the obese adolescents. Adiponectin was significantly lower in the obese group than the control group ($3.3{\pm}1.9{\mu}g/mL$ vs $5.0{\pm}1.4{\mu}g/mL$). Leptin had positive correlations with obesity index, BMI, and IL-6. Conclusion : In obese adolescents, leptin, TNF-${\alpha}$, IL-6, and insulin might be important mediators of obesity. Further clinical research is necessary to ascertain leptin as a predictor of cardiovascular diseases and to develop a guideline for clinical intervention.

목 적 : 비만은 지방세포의 축적과 인슐린 내성으로 제 2형 당뇨병을 초래하고, 고 인슐린혈증과 고혈당이 염증 과정의 전구 물질과 함께 작용하여 혈관 내피의 이상, 혈청 지질의 이상, 고혈압과 혈관 염증을 일으켜 동맥경화와 심혈관 질환을 야기하는 것으로 알려져 왔다. Leptin은 adiopnectin과 함께 지방 세포로부터 생산되는 가장 풍부한 adipocytokine으로서, 일차적으로는 식욕 조절과 체내 지방 축적 조절의 기능을 하지만, IL-6, IL-12, TNF-${\alpha}$와 같은 다른 사이토카인과 함께 염증과정의 전구 물질이 되며 여러 면역 관련 질환에서 중요한 매개체가 된다. 이번 연구에서는 비만 청소년에서 leptin과 여러 cytokine과의 상관관계를 알아보고자 하였다. 방 법 : 16세 이상부터 18세 미만의 66명의 중등도 이상의 비만 청소년을 대상군으로 하였고, 같은 연령의 정상 청소년 26명을 대조군으로 하였다. 신장, 체중을 이용하여 비만도와 체질량지수를 산출하였고, 혈청 지질, 간 효소치를 측정하였다. 효소면역 측정법을 이용하여 IL-6, TNF-${\alpha}$를 측정하였고, 방사면역 측정법을 이용하여 adiponectin, leptin, 인슐린을 측정하였다. 이 후 leptin과 각 측정치와의 상관성을 알아보았다. 결 과 : Leptin은 비만군에서 대조군보다 유의하게 높았고, TNF-${\alpha}$와 IL-6도 비만군에서 대조군보다 유의하게 높았다. 인슐린도 비만군에서 대조군보다 유의하게 높았고 adiponectin은 비만군에서 유의하게 낮았다. Leptin은 비만도, 체질량지수, IL-6과 유의한 양의 상관관계를 보였으며, 또한 IL-6와 TNF-${\alpha}$간에 유의한 양의 상관관계를 보였다. 결 론 : 비만 청소년에서 leptin, TNF-${\alpha}$, IL-6와 같은 cytokine과 insulin이 성인병으로 진행되는데 중요한 요소가 될 것이며, leptin을 성인병의 예측 인자 및 임상치료의 척도로 사용하기 위해 더 많은 연구가 필요할 것으로 생각된다.

Keywords

References

  1. Korner A, Kratzsch J, Gausche R, Schaab M, Erbs S, Kiess W. New predictors of the metabolic syndrome in childrenrole of adipocytokines. Pediatr Res 2007;61:640-5 https://doi.org/10.1203/01.pdr.0000262638.48304.ef
  2. Valle M, Gascón F, Martos R, Ruz FJ, Bermudo F, Morales R, et al. Metabolic cardiovascular syndrome in obese prepubertal children: the role of high fasting insulin levels. Metab 2002;51:423-8 https://doi.org/10.1053/meta.2002.31319
  3. Korner A, Bluher S, Kapellen T, Garten A, Klammt J, Kratzsch J, Kiess W. Obesity in childhood and adolescence: a review in the interface between adipocyte physiology and clinical challenges. Hormones (Athens) 2005;4:189-99 https://doi.org/10.14310/horm.2002.11158
  4. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004;92: 347-55 https://doi.org/10.1079/BJN20041213
  5. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005;115:1111-9 https://doi.org/10.1172/JCI25102
  6. Vettor R, Milan G, Rossato M, Federspil G. Review article: adipocytokines and insulin resistance. Aliment Pharmacol Ther 2005;22 Suppl 2:3-10 https://doi.org/10.1111/j.1365-2036.2005.02587.x
  7. Kusminski CM, Mcternan PG, Kumar S. Role of resistin in obesity, insulin resistance and Type II diabetes. Clin Sci (Lond) 2005;109:243-56 https://doi.org/10.1042/CS20050078
  8. Rahmouni K, Haynes WG. Leptin and the cardiovascular system. Recent Prog Horm Res 2004;59:225-44 https://doi.org/10.1210/rp.59.1.225
  9. Muoio DM, Dohm GL. Peripheral metabolic actions of leptin. Best Pract Res Clin Endocrinol Metab 2002;16:653-66 https://doi.org/10.1053/beem.2002.0223
  10. Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 2006;6:772-83 https://doi.org/10.1038/nri1937
  11. Nemet D, Wang P, Funahashi T, Matsuzawa Y, Tanaka S, Engelman L, et al. Adipocytokines, body composition, and fitness in children. Pediatr Res 2003;53:148-52 https://doi.org/10.1203/00006450-200301000-00025
  12. Kratzsch J, Lammert A, Bottner A, Seidel B, Mueller G, Thiery J, et al. Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence. J Clin Endocrinol Metabol 2002;87:4587-94 https://doi.org/10.1210/jc.2002-020001
  13. Kempf AM, Strother ML, Li C, Kaur H, Huang TT. Leptin as a marker of body fat and hyperinsulinemia in college students. J Am Coll Health 2006;55:175-80 https://doi.org/10.3200/JACH.55.3.175-180
  14. Venner AA, Lyon ME, Doyle-Baker PK. Leptin: a potential biomarker for childhood obesity? Clin Biochem 2006;39: 1047-56 https://doi.org/10.1016/j.clinbiochem.2006.07.010
  15. Otero M, Lago R, Lago F, Casanueva FF, Dieguez C, Gómez-Reino JJ, et al. Leptin, from fat to inflammation: old questions and insights. FEBS Lett 2005;579:295-301 https://doi.org/10.1016/j.febslet.2004.11.024
  16. Dubey S, Kabra M, Bajpai A, Pandey RM, Hasan M, Gautam RK, et al. Serum leptin levels in obese Indian children relation to clinical and biochemical parameters. Indian Pediatr 2007;44:257-62
  17. Shin MJ, Park E. Plasma levels of leptin are associated with the plasma levels of LDL conjugated dienes in children. Ann Nutr Metab 2007;51:1-6
  18. Lago F, Dieguez C, Gomez-Reino J, Gualillo O. The emerging role of adipokines as mediators of inflammation and immune responses. Cytokine Growth Factor Rev 2007;18: 313-25 https://doi.org/10.1016/j.cytogfr.2007.04.007
  19. Vendrell J, Broch M, Vilarrasa N, Molina A, Gomez JM, Gutierrez C, et al. Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. Obes Res 2004;12:962-71 https://doi.org/10.1038/oby.2004.118
  20. Dzienis-Straczkowska S, Straczkowski M, Szelachowska M, Stepien A, Kowalska I, Kinalska I. Soluble tumor necrosis factor-alpha receptors in young obese subjects with normal and impaired glucose tolerance. Diabetes Care 2003;26:875-80 https://doi.org/10.2337/diacare.26.3.875
  21. Valle M, Martos R, Gascon F, Canete R, Zafra MA. Morales R. Low-grade systemic inflammation, hypoadiponectinemia and a high concentration of leptin are present in very young obese children, and correlate with metabolic syndrome. Diabetes Metab 2005;31:55-62 https://doi.org/10.1016/S1262-3636(07)70167-2
  22. Aycan Z, Berberoğlu M, Ocal G, Evliyaoglu O, Adiyaman P, Deda G, et al. Relationship between plasma leptin, insulin and tumor necrosis factor alpha in obese children. J Pediatr Endocrinol Metab 2005;18:275-84
  23. Sinha MK, Caro JF. Clinical aspects of leptin. Vitam Horm 1998;54:1-30 https://doi.org/10.1016/S0083-6729(08)60919-X
  24. Fleisch AF, Agarwal N, Roberts MD, Han JC, Theim KR, Vexler A, et al. Influence of serum leptin on weight and body fat growth in children at high risk for adult obesity. J Clin Endocrinol Metab 2007;92:948-54 https://doi.org/10.1210/jc.2006-1390
  25. Liuzzi A, Savia G, Tagliaferri M, Lucantoni R, Berselli ME, Petroni ML, et al. Serum leptin concentration in moderate and severe obesity: relationship with clinical, anthropometric and metabolic factors. Int J Obes Relat Metab Disord 1999; 23:1066-73 https://doi.org/10.1038/sj.ijo.0801036
  26. Ostlund RE Jr, Yang JW, Klein S, Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab 1996;81:3909-13 https://doi.org/10.1210/jc.81.11.3909
  27. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995;270:26746-9 https://doi.org/10.1074/jbc.270.45.26746
  28. Wolf G. Adiponectin: a regulator of energy homeostasis. Nutr Rev 2003;61:290-2 https://doi.org/10.1301/nr.2003.aug.290-292
  29. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adiposespecific gene dysregulated in obesity. J Biol Chem 1996; 271:10697-703 https://doi.org/10.1074/jbc.271.18.10697
  30. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001;86:1930-5 https://doi.org/10.1210/jc.86.5.1930
  31. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999;100:2473-6 https://doi.org/10.1161/01.CIR.100.25.2473
  32. Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem 2002;277:37487-91 https://doi.org/10.1074/jbc.M206083200
  33. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 2003;278:2461-8 https://doi.org/10.1074/jbc.M209033200
  34. Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamota Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001;103:1057-63 https://doi.org/10.1161/01.CIR.103.8.1057
  35. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res 2002;10:1104-10 https://doi.org/10.1038/oby.2002.150
  36. Stefan N, Bunt JC, Salbe AD, Funahashi T, Matsuzawa Y, Tataranni PA. Plasma adiponectin concentrations in children: relationships with obesity and insulinemia. J Clin Endocrinol Metab 2002;87:4652-6 https://doi.org/10.1210/jc.2002-020694

Cited by

  1. OLETF 당뇨모델동물을 이용한 맥문동 추출물(LP9M80-H)의 당뇨질환에 대한 효능 vol.22, pp.5, 2008, https://doi.org/10.5352/jls.2012.22.5.634
  2. 유전성 비만 마우스에 대한 아프리칸 망고 추출물의 항비만 효과 vol.43, pp.10, 2008, https://doi.org/10.3746/jkfn.2014.43.10.1477
  3. 식방풍잎(Peucedanum japonicum Thunberg L.)의 물추출물이 3T3-L1 세포와 고지방식이로 유도된 마우스에서 항비만 효과 vol.29, pp.1, 2008, https://doi.org/10.7732/kjpr.2016.29.1.001
  4. 호박즙, 옥수수수염차, 팥차 및 혼합물이 식이유도 비만동물모델에서 체중과 항산화 활성에 미치는 영향 vol.45, pp.9, 2016, https://doi.org/10.3746/jkfn.2016.45.9.1239
  5. Platycodon grandiflorum Extract Reduces High-Fat Diet-Induced Obesity Through Regulation of Adipogenesis and Lipogenesis Pathways in Mice vol.22, pp.10, 2008, https://doi.org/10.1089/jmf.2018.4370