Association of serum bilirubin, selected iron status indicators and body composition in non-obese, normoglycemic subjects
Abstract
Background: Recently cardiometabolic risk reduction has been observed in patients with slightly elevated
bilirubin concentration, as well as increased risk in subjects with excessive iron reserves. The aim of this
study was to evaluate the relationship between overweight and/or abdominal obesity, serum bilirubin and
selected iron status indicators levels in non-obese subjects.
Methods: The study group consisted of 80 healthy, non-obese subjects aged 25–40 years. In all subjects
total and direct bilirubin (T-BIL, D-BIL), iron (Fe), transferrin (TRSF), ferritin (FERR) and hepcidin (HEPC)
measurements were performed. Anthropometric parameters (BMI, waist circumference, WHR) were
measured and body composition (% of body fat, muscles and level of visceral fat) was evaluated using
body segment analyzer.
Results: Men showed significantly higher values of waist circumference, WHR, muscle mass, visceral fat
level and FERR and HEPC concentrations, compared to women. Lower concentrations of T-BIL, D-BIL and
higher concentration of FERR, HEPC occurred in the overweight group. In all subjects and in the overweight
group T-BIL, D-BIL showed negative correlations with BMI, waist circumference, fat mass and visceral fat
level, while for FERR, HEPC those correlations were positive. Overweight subjects had an approximately
4-fold higher incidence of low T-BIL, D-BIL levels (p < 0,001), as well as nearly 2-fold higher incidence of
high transferrin level (p = 0,02).
Conclusions: Overweight subjects have lower bilirubin levels and higher levels of factors potentially contributing
to increased oxidative stress, for example ferritin and hepcidin. Serum bilirubin, ferritin and hepcidin
concentration are related to body composition indicators, particullary fat mass and visceral fat level.
Keywords: bilirubinantioxidantiron metabolismoverweightobesity
References
- Troughton J, Woodside J, Young I, et al. Bilirubin and coronary heart disease risk in the Prospective Epidemiological Study of Myocardial Infarction (PRIME). European Journal of Cardiovascular Prevention & Rehabilitation. 2016; 14(1): 79–84.
- Wiwanitkit V. Energy change in the formation of conjugated bilirubin: a possible responsive mechanism for liver cell pathology. Rev Esp Enferm Dig. 2007; 99(2): 94–95.
- Leszczyńska-Gołąbek I, Kuśnierz-Cabala B. Diagnostyka laboratoryjna chorób przewodu pokarmowego wątroby i trzustki. In: Dembińska-Kieć A, Naskalski JW ed. Diagnostyka laboratoryjna z elementami biochemii klinicznej. Elsevier Urban & Partner, Wrocław. ; 2015: 753–759.
- Bergmann K, Pachota E, Odrowąż-Sypniewska G. Association of serum total bilirubin with traditional and novel cardiovascular risk factors in apparently healthy subjects. Folia Med Coper. 2015; 3(1): 26–31.
- Edison ES, Bajel A, Chandy M. Iron homeostasis: new players, newer insights. Eur J Haematol. 2008; 81(6): 411–424.
- Podolecki T, Wasilewski J, Poloński L. Potencjalna rola żelaza w etiopatogenezie choroby wieńcowej. Chor Serca i Naczyń. 2009; 6(4): 180–183.
- Abraham NG, Kappas A. Pharmacological and Clinical Aspects of Heme Oxygenase. Pharmacological Reviews. 2008; 60(1): 79–127.
- Maghzal GJ, Leck MC, Collinson E, et al. Limited role for the bilirubin-biliverdin redox amplification cycle in the cellular antioxidant protection by biliverdin reductase. J Biol Chem. 2009; 284(43): 29251–29259.
- Kawamura K, Ishikawa K, Wada Y, et al. Bilirubin from heme oxygenase-1 attenuates vascular endothelial activation and dysfunction. Arterioscler Thromb Vasc Biol. 2005; 25(1): 155–160.
- McArdle PF, Whitcomb BW, Tanner K, et al. Association between bilirubin and cardiovascular disease risk factors: using Mendelian randomization to assess causal inference. BMC Cardiovasc Disord. 2012; 12: 16.
- Endler G, Hamwi A, Sunder-Plassmann R, et al. Is low serum bilirubin an independent risk factor for coronary artery disease in men but not in women? Clin Chem. 2003; 49(7): 1201–1204.
- Choi JW, Kim SK, Pai SH. Changes in serum lipid concentrations during iron depletion and after iron supplementation. Ann Clin Lab Sci. 2001; 31(2): 151–156.
- Oliński R, Jurgowiak M. Żelazo, wolne rodniki i oksydacyjne uszkodzenia DNA a choroba miażdżycowa. Acta Angiol. 2002; 8(2): 37–44.
- Zeid AA, Saka MEl, Abdalfattah A, et al. Potential factors contributing to poor iron status with obesity. Alexandria Journal of Medicine. 2014; 50(1): 45–48.
- Mayer M. Association of serum bilirubin concentration with risk of coronary artery disease. Clin Chem. 2000; 46(11): 1723–1727.
- Hosick PA, Stec DE. Heme oxygenase, a novel target for the treatment of hypertension and obesity? Am J Physiol Regul Integr Comp Physiol. 2012; 302(2): R207–R214.
- Przybyszewska J, Żekanowska E, Kędziora-Kornatowska K, et al. Comparison of serum prohepcidin and iron metabolism parameters in obese and non-obese elderly individuals. Endokrynol Pol. 2013; 64(4): 272–277.
- Andersson C, Weeke P, Fosbøl EL, et al. SCOUT Executive Steering Committee, SCOUT investigators. Acute effect of weight loss on levels of total bilirubin in obese, cardiovascular high-risk patients: an analysis from the lead-in period of the Sibutramine Cardiovascular Outcome trial. Metabolism. 2009; 58(8): 1109–1115.
- Swift DL, Johannsen NM, Earnest CP, et al. Effect of different doses of aerobic exercise training on total bilirubin levels. Med Sci Sports Exerc. 2012; 44(4): 569–574.
- Maruhashi T, Soga J, Fujimura N, et al. Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in Gilbert syndrome. Circulation. 2012; 126(5): 598–603.
- Jehn M, Clark JM, Guallar E. Serum ferritin and risk of the metabolic syndrome in U.S. adults. Diabetes Care. 2004; 27(10): 2422–2428.
- You SA, Wang Q. Ferritin in atherosclerosis. Clinica Chimica Acta. 2005; 357(1): 1–16.
- de Godoy MF, Takakura IT, Machado RD, et al. Serum ferritin and obstructive coronary artery disease: angiographic correlation. Arq Bras Cardiol. 2007; 88(4): 430–433.
- Escobar-Morreale HF, Luque-Ramirez M, Alvarez-Blasco F, et al. Body Iron Stores Are Increased in Overweight and Obese Women With Polycystic Ovary Syndrome. Diabetes Care. 2005; 28(8): 2042–2044.
- Williams MJA, Poulton R, Williams S. Relationship of serum ferritin with cardiovascular risk factors and inflammation in young men and women. Atherosclerosis. 2002; 165(1): 179–184.
- Nead KG, Halterman JS, Kaczorowski JM, et al. Overweight children and adolescents: a risk group for iron deficiency. Pediatrics. 2004; 114(1): 104–108.
- Pinhas-Hamiel O, Newfield RS, Koren I, et al. Greater prevalence of iron deficiency in overweight and obese children and adolescents. Int J Obes Relat Metab Disord. 2003; 27(3): 416–418.
- Zafon C, Lecube A, Simó R. Iron in obesity. An ancient micronutrient for a modern disease. Obes Rev. 2010; 11(4): 322–328.
- Cheng HL, Bryant CE, Rooney KB, et al. Iron, hepcidin and inflammatory status of young healthy overweight and obese women in Australia. PLoS One. 2013; 8(7): e68675.
- Martinelli N, Traglia M, Campostrini N, et al. Increased serum hepcidin levels in subjects with the metabolic syndrome: a population study. PLoS One. 2012; 7(10): e48250.