Bilirubin is independently associated with oxidized LDL levels in young obese patients

Diabetology & Metabolic Syndrome

Luís Belo⁷  Alice Santos-Silva⁷  Carla Rêgo⁵  Helena Ferreira Mansilha³  Jorge Mota⁶  Luísa Aires²  Petronila Rocha-Pereira⁸  Elísio Costa⁷  Elsa Bronze-da-Rocha⁷  Diana Gomes⁴  Cristina Catarino⁷  Susana Coimbra¹  Ana Inês Alves⁴  Henrique Nascimento⁷ 

[1] CESPU, Institute for Research and Advanced Training in Health Sciences and Technologies, Gandra, Portugal;High Education Institute from Maia (ISMAI), S. Pedro Avioso, Portugal;Childhood and Adolescence Department/Pediatric Service of Porto Hospital Centre, Porto, Portugal;Instituto de Investigaçãoe Inovação em Saúde (Institute for Research and Innovation in Health), Universidade do Porto, Porto, Portugal;Children and Adolescent Centre, CUF Hospital. CINTESIS. Faculty of Medicine, University of Porto, Porto, Portugal;Research Centre in Physical Activity, Health and Leisure – CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal;Biological Science Department, Faculty of Pharmacy, University of Porto, Porto, Portugal;Health Science Research Centre, University of Beira Interior, Covilhã, Portugal

关键词: Pediatric obesity;    Atherosclerosis;    Oxidative stress;    Oxidized-LDL;    Bilirubin;   

Others  :  1128672
DOI  :  10.1186/1758-5996-7-4

 received in 2014-11-11, accepted in 2015-01-14,  发布年份 2015

【 摘 要 】

Background

Bilirubin can prevent lipid oxidation in vitro, but the association in vivo with oxidized low-density lipoprotein (Ox-LDL) levels has been poorly explored. Our aim is to the association of Ox-LDL with total bilirubin (TB) levels and with variables related with metabolic syndrome and inflammation, in young obese individuals.

Findings

125 obese patients (13.4 years; 53.6% females) were studied. TB, lipid profile including Ox-LDL, markers of glucose metabolism, and levels of C-reactive protein (CRP) and adiponectin were determined. Anthropometric data was also collected.

In all patients, Ox-LDL correlated positively with BMI, total cholesterol, LDLc, triglycerides (TG), CRP, glucose, insulin and HOMA_IR; while inversely with TB and HDLc/Total cholesterol ratio (P < 0.05 for all). In multiple linear regression analysis, LDLc, TG, HDLc and TB levels were significantly associated with Ox-LDL (standardized Beta: 0.656, 0.293, −0.283, −0.164, respectively; P < 0.01 for all). After removing TG and HDLc from the analysis, HOMA_IR was included in the regression model. In this new model, LDLc remained the best predictor of Ox-LDL levels (β = 0.665, P < 0.001), followed by TB (β = −0.202, P = 0.002) and HOMA_IR (β = 0.163, P = 0.010).

Conclusions

Lower bilirubin levels may contribute to increased LDL oxidation in obese children and adolescents, predisposing to increased cardiovascular risk.

【 授权许可】

   
2015 Nascimento et al.; licensee BioMed Central.

【 参考文献 】

• [1]Wu TW, Fung KP, Wu J, Yang CC, Weisel RD: Antioxidation of human low density lipoprotein by unconjugated and conjugated bilirubins. Biochem Pharmacol 1996, 51:859-862.
• [2]Boon AC, Hawkins CL, Bisht K, Coombes JS, Bakrania B, Wagner KH, et al.: Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome. Free Radic Biol Med 2012, 52:2120-2127.
• [3]Stojanov M, Stefanovic A, Dzingalasevic G, Ivanisevic J, Miljkovic M, Mandic-Radic S, et al.: Total bilirubin in young men and women: association with risk markers for cardiovascular diseases. Clin Biochem 2013, 46:1516-1519.
• [4]Horsfall LJ, Nazareth I, Petersen I: Cardiovascular events as a function of serum bilirubin levels in a large, statin-treated cohort. Circulation 2012, 126:2556-2564.
• [5]McArdle PF, Whitcomb BW, Tanner K, Mitchell BD, Shuldiner AR, Parsa A: Association between bilirubin and cardiovascular disease risk factors: using Mendelian randomization to assess causal inference. BMC Cardiovasc Disord 2012, 12:16. BioMed Central Full Text
• [6]Lin LY, Kuo HK, Hwang JJ, Lai LP, Chiang FT, Tseng CD, et al.: Serum bilirubin is inversely associated with insulin resistance and metabolic syndrome among children and adolescents. Atherosclerosis 2009, 203:563-568.
• [7]Nascimento H, Costa E, Rocha S, Lucena C, Rocha-Pereira P, Rego C, et al.: Adiponectin and markers of metabolic syndrome in obese children and adolescents: impact of 8-mo regular physical exercise program. Pediatr Res 2014, 76:159-165.
• [8]Norris AL, Steinberger J, Steffen LM, Metzig AM, Schwarzenberg SJ, Kelly AS: Circulating oxidized LDL and inflammation in extreme pediatric obesity. Obesity (Silver Spring) 2011, 19:1415-1419.
• [9]Ryder JR, Vega-Lopez S, Djedjos CS, Shaibi GQ: Abdominal adiposity, insulin resistance, and oxidized low-density lipoproteins in Latino adolescents. Diabetol Metab Syndr 2013, 5:72. BioMed Central Full Text
• [10]National Center for Health Statistics Centers for Disease Control and Prevention Hyattsville M: ANALYTIC AND REPORTING GUIDELINES: The Third National Health and Nutrition Examination Survey, NHANES III (1988–94). Book ANALYTIC AND REPORTING GUIDELINES: The Third National Health and Nutrition Examination Survey, NHANES III (1988–94) 1996.
• [11]Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28:412-419.
• [12]Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972, 18:499-502.
• [13]Chait A, Brazg RL, Tribble DL, Krauss RM: Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B. Am J Med 1993, 94:350-356.
• [14]de Graaf J, Hak-Lemmers HL, Hectors MP, Demacker PN, Hendriks JC, Stalenhoef AF: Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects. Arterioscler Thromb 1991, 11:298-306.
• [15]Kontush A: HDL-mediated mechanisms of protection in cardiovascular disease. Cardiovasc Res 2014, 103:341-349.
• [16]Mertens A, Holvoet P: Oxidized LDL and HDL: antagonists in atherothrombosis. Faseb J 2001, 15:2073-2084.
• [17]do Sameiro-Faria M, Kohlova M, Ribeiro S, Rocha-Pereira P, Teixeira L, Nascimento H, et al.: Potential cardiovascular risk protection of bilirubin in end-stage renal disease patients under hemodialysis. Biomed Res Int 2014, 2014:175286.
• [18]Kelly AS, Jacobs DR Jr, Sinaiko AR, Moran A, Steffen LM, Steinberger J: Relation of circulating oxidized LDL to obesity and insulin resistance in children. Pediatr Diabetes 2010, 11:552-555.
• [19]Belo L, Nascimento H, Kohlova M, Bronze-da-Rocha E, Fernandes J, Costa E, et al.: Body fat percentage is a major determinant of total bilirubin independently of UGT1A1*28 polymorphism in young obese. PLoS One 2014, 9:e98467.
• [20]Nascimento H, Silva L, Lourenco P, Weinfurterova R, Castro E, Rego C, et al.: Lipid profile in Portuguese obese children and adolescents: interaction of apolipoprotein E polymorphism with adiponectin levels. Arch Pediatr Adolesc Med 2009, 163:1030-1036.