Obez Türk çocuklarında plazma adiponektin ve plazminojen aktivatör inhibitor-1 düzeyleri

Year 2019, Volume: 3 Issue: 2, 102 - 116, 30.06.2019

Ferda Ozbay Leyla Tumer Fatih Süheyl Ezgü Asburce Olgac Alev Hasanoglu

https://doi.org/10.33716/bmedj.567409

Abstract

Giriş: Obezitenin tek başına ateroskleroz için bir risk faktörü olduğu
bilinmektedir. Obezite ve ateroskleroz ilişkisi ile ilgili bilinen başlıca
faktörler dislipidemi, insülin rezistansı ve insülin duyarlılığını artırıcı bir
adipositokin olan adiponektin (ADPN) eksikliğidir. Bu çalışmada, obez
çocuklarda adiponektin düzeylerinin araştırılması ve adiponektin düzeyleri ile
ateroskleroza yatkınlık oluşturduğu bilinen başka faktörlerin ilişkilerinin
değerlendirilmesi amaçlanmıştır.

Gereçler ve yöntem: 30 obez çocuk hastanın ve 28 sağlıklı çocuğun plazma
örneklerinden ADPN, plazminojen aktivatör inhbitor-1 (PAI-1), lipid profili, insülin
ve tam kan örneklerinden hemoglobin A1c (HbA1c) düzeyleri belirlendi ve bu
faktörlerin birbirleri ile ilişkileri araştırıldı. Obez hasta grubunda oral
glukoz tolerans testi (OGTT) uygulandı ve OGTT’nin 2. saatinde ADPN ve PAI-1 düzeyleri
tekrar değerlendirildi.

Sonuçlar: Obez hasta grubunda, bazal ADPN ve PAI-1 düzeyleri, OGTT’nin
2. saatinde elde edilen değerlere göre daha düşük tesbit edildi. Bazal ADPN
düzeyleri, vücut kitle indeksi, trigliserid düzeyleri, çok düşük dansiteli lipoprotein
(VLDL) ve insulin düzeyleri ile negatif korelasyon göstermekteydi. Postprandial
elde edilen ADPN ve PAI-1 bazal değerlere göre anlamlı olarak yüksek tespit
edildi. Postprandial PAI-1 ve yüksek dansiteli lipoprotein (HDL) arasında ve
postprandial ADPN ile insulin ve trigliserid düzeyleri arasında negatif
korelasyon tesbit edildi. Trigliserid ve insulin düzeylerindeki değişiklikler
ADPN’i negatif yönde etkilerken, HbA1c’deki değişiklikler pozitif yönde
etkilemekteydi.

Sonuç: Çalışmamız plazma ADPN düzeylerinin atheroskleroz yatkınlığını
gösteren bir belirteç olarak kullanılabileceğini ortaya koymaktadır.

Keywords

Çocukluk çağı obezitesi, adiponectin, plazminojen aktivatör inhibitör-1

Plasma levels of adiponectin and plasminogen activator inhibitor-1 in Turkish obese children

Abstract

Introduction: It is known that obesity itself is a risk factor for
atherosclerosis. Dyslipidemia, insulin resistance and the deficiency of the
adiponectin (ADPN), which is an adipocytokine increasing the insulin
sensitivity, are the main factors known for their relations with the obesity
and atherosclerosis. This study aimed to determine the levels of plasma ADPN in
obese children and its relationship with several other factors associated with
atherosclerosis.

Materials and Method: Plasma levels of ADPN, plasminogen activator
inhbitor-1 (PAI-1), lipids and insulin and blood hemoglobin A1c (HbA1c) levels
were measured and their relations with each other were determined in 30 obese
and 28 healthy children. Oral glucose tolerance test (OGTT) was performed to
obese children and ADPN and PAI-1 levels were rechecked at the second hour of
OGTT.

Results: In obese children, the basal ADPN and PAI-1 levels were lower, than
their levels obtained 2 hours after the OGTT. Basal ADPN levels showed negative
correlation with the body mass index, and triglyceride, very low density
lipoprotein (VLDL) and insulin levels. Negative correlation was also detected
between the postprandial PAI-1 and high density lipoprotein (HDL), and between
plasma ADPN and insulin and triglyceride levels. While the changes in
triglyceride and insulin levels negatively affected the ADPN, the changes in
HbA1c affected ADPN positively.

Conclusion: Our study indicates that, plasma ADPN level can be used as a
follow up marker for atherosclerosis.

Keywords

Childhood obesity, adiponectin, plasminogen activator inhibitor-1

References

• 1) Balagopal PB, de Ferranti SD, Cook S, Daniels SR, Gidding SS, Hayman LL, et al. American Heart Association Committee on Atherosclerosis Hypertension and Obesity in Youth of the Council on Cardiovascular Disease in the Young; Council on Nutrition, Physical Activity and Metabolism; Council on Epidemiology and Prevention. Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the American Heart Association. Circulation. 2011 Jun 14;123(23):2749-69.
• 2) Fu J, Li Y, Esangbedo IC, Li G, Feng D, Li L, Xu L, et al. Circulating Osteonectin and Adipokine Profiles in Relation to Metabolically Healthy Obesity in Chinese Children: Findings From BCAMS. J Am Heart Assoc. 2018 Dec 4;7(23):e009169.
• 3) Sjöholm A, Nyström T. Endothelial inflammation in insulin resistance. Lancet. 2005 Feb 12-18;365(9459):610-2.
• 4) Okamoto Y, Arita Y, Nishida M, Muraguchi M, Ouchi N, Takahashi M, et al. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res 2000; 32: 47-50
• 5) Sudi KM, Gallistl S, Weinhandl G, Muntean W, Borkenstein MH. Relationship between plasminogen activator inhibitor-1 antigen, leptin, and fat mass in obese children and adolescents. Metabolism 2000; 49: 890-895
• 6) Tyson N, Frank M. Childhood and adolescent obesity definitions as related to BMI, evaluation and management options. Best Pract Res Clin Obstet Gynaecol. 2018 Apr;48:158-164.
• 7) American Diabetes Association. 12. Children and Adolescents: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S126-S136.
• 8) Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257: 79-83.
• 9) 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: 148-152.
• 10) 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: 37487-37491.
• 11) Ding W, Cheng H, Chen F, Yan Y, Zhang M, Zhao X, et al. Adipokines are Associated With Hypertension in Metabolically Healthy Obese (MHO) Children and Adolescents: A Prospective Population-Based Cohort Study. J Epidemiol. 2018 Jan 5;28(1):19-26.
• 12) Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999; 100: 2473-6247
• 13) De Taeye B, Smith LH, Vaughan DE. Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease. Curr Opin Pharmacol. 2005 Apr;5(2):149-54.
• 14) Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20: 1595-1599.
• 15) Stefan N, Stumvoll M: Adiponectin-its role in metabolism and beyond. Horm Metab Res 2002; 34: 469-474
• 16) 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: 1930-1935
• 17) Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res 10: 2002; 1104-1110
• 18) Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2002; 290: 1084-1089
• 19) Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 2001; 50: 1126-1133
• 20) Mallamaci F, Zoccali C, Cuzzola F, Tripepi G, Cutrupi S, Parlongo S, et al. Adiponectin in essential hypertension. J Nephrol 2002;15: 507-511
• 21) Ravussin E: Adiponectin enhances insulin action by decreasing ectopic fat deposition. Pharmacogenomics J 2002; 2: 4-7
• 22) Agostinis-Sobrinho C, Santos R, Moreira C, Abreu S, Lopes L, Oliveira-Santos J, et al. Association between serum adiponectin levels and muscular fitness in Portuguese adolescents: LabMed Physical Activity Study. Nutr Metab Cardiovasc Dis. 2016 Jun;26(6):517-24
• 23) Valle M, Gascon F, Martos R, Ruz FJ, Bermudo F, Ríos R, et al. Infantile obesity: a situation of atherothrombotic risk? Metabolism 2000; 49: 672-675
• 24) Juhan-Vague I, Alessi MC: Regulation of fibrinolysis in the development of atherothrombosis: role of adipose tissue. Thromb Haemost 1999; 82: 832-836
• 25) Samad F, Uysal KT, Wiesbrock SM, Pandey M, Hotamisligil GS, Loskutoff DJ. Tumor necrosis factor alpha is a key component in the obesity-linked elevation of plasminogen activator inhibitor 1. Proc Natl Acad Sci USA 1999; 96: 6902-6907
• 26) Sartori MT, Vettor R, De Pergola G, De Mitrio V, Saggiorato G, Della Mea P, et al. Role of the 4G/5G polymorphism of PaI-1 gene promoter on PaI-1 levels in obese patients: influence of fat distribution and insulin-resistance. Thromb Haemost 2001; 86: 1161-1169
• 27) Sakamoto T, Woodcock-Mitchell J, Marutsuka K, Mitchell JJ, Sobel BE, Fujii S. TNF-alpha and insulin, alone and synergistically, induce plasminogen activator inhibitor-1 expression in adipocytes. Am J Physiol 1999; 276: 1391-1397