Korean J Fam Pract. 2018; 8(3): 423-428  https://doi.org/10.21215/kjfp.2018.8.3.423
Association between Nonalcoholic Fatty Liver Disease and Concentration of Copper and Zinc in Hair Tissue in Korean Adults
Yuri Kwon, Kyung-Chae Park*, Seung-Gun Park, Moon-Hee Kim, Hyejin Oh, Hyewon Kim
Department of Family Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
Kyung-Chae Park
Tel: +82-31-780-5360, Fax: +82-31-780-5944
E-mail: kc829@cha.ac.kr
ORCID: http://orcid.org/0000-0002-5453-808X
Received: May 31, 2017; Revised: August 4, 2017; Accepted: August 15, 2017; Published online: June 20, 2018.
© The Korean Academy of Family Medicine. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Nonalcoholic fatty liver disease (NAFLD) has been reported to be related with metabolic disorders. Although copper (Cu) and zinc (Zn) are known as essential elements for the function of many proteins related to metabolic disorders, the relationship between NAFLD and concentrations of Cu and Zn is not well established. The aim of this study was to evaluate the association between NAFLD and the concentrations of Cu and Zn in hair tissue in Korean adults.
Methods: This cross-sectional study included 438 adults (220 men and 218 women) who participated in a medical examination program from January 2010 to December 2011. For this study, 219 subjects who satisfied the NAFLD criteria and 219 healthy controls were included. The participants were screened for fatty liver by using abdominal ultrasonography and for Cu and Zn levels by using hair tissue samples.
Results: The hair Cu concentrations in patients with NAFLD were lower than those in the control subjects (2.9±4.2 vs. 5.4±7.8 mg%; P<0.001), which was confirmed in the logistic regression model that was adjusted for age, sex, and potential confounding parameters (model 3, odds ratio 0.934; 95% confidence interval 0.885–0.986; P=0.013). However, although the hair Zn concentrations in patients with NAFLD were lower than those in the control subjects in the crude model (21.1±12.1 vs. 17.1±7.6 mg%; P<0.001), no significance was found in the logistic regression model.
Conclusion: Reduced hair Cu concentrations were found in the Korean adults with NAFLD, which suggests that Cu availability may be involved in the development of NAFLD or that Cu level may decrease in response to NAFLD.
Keywords: Non-Alcoholic Fatty Liver Disease; Fatty Liver; Copper; Zinc; Hair Mineral; Metabolic Risk Factors
  1. Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis 2001; 21: 3-16.
    Pubmed CrossRef
  2. Ekstedt M, Franzén LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: 865-73.
    Pubmed CrossRef
  3. Cheung O, Sanyal AJ. Abnormalities of lipid metabolism in nonalcoholic fatty liver disease. Semin Liver Dis 2008; 28: 351-9.
    Pubmed CrossRef
  4. Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis 2008; 28: 370-9.
    Pubmed CrossRef
  5. Sakiyama H, Fujiwara N, Yoneoka Y, Yoshihara D, Eguchi H, Suzuki K. Cu,Zn-SOD deficiency induces the accumulation of hepatic collagen. Free Radic Res 2016; 50: 666-77.
    Pubmed CrossRef
  6. al-Othman AA, Rosenstein F, Lei KY. Copper deficiency alters plasma pool size, percent composition and concentration of lipoprotein components in rats. J Nutr 1992; 122: 1199-204.
    Pubmed CrossRef
  7. Sanyal AJ. Mechanisms of disease: pathogenesis of nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 2005; 2: 46-53.
    Pubmed CrossRef
  8. Schnabl B, Czech B, Valletta D, Weiss TS, Kirovski G, Hellerbrand C. Increased expression of zinc finger protein 267 in non-alcoholic fatty liver disease. Int J Clin Exp Pathol 2011; 4: 661-6.
    Pubmed KoreaMed
  9. Park SH, Jeon WK, Kim SH, Kim HJ, Park DI, Cho YK, et al. Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults. J Gastroenterol Hepatol 2006; 21: 138-43.
    Pubmed CrossRef
  10. Ko WS, Guo CH, Yeh MS, Lin LY, Hsu GS, Chen PC, et al. Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C. World J Gastroenterol 2005; 11: 4697-702.
    KoreaMed CrossRef
  11. Matsuoka S, Matsumura H, Nakamura H, Oshiro S, Arakawa Y, Hayashi J, et al. Zinc supplementation improves the outcome of chronic hepatitis C and liver cirrhosis. J Clin Biochem Nutr 2009; 45: 292-303.
    Pubmed KoreaMed CrossRef
  12. Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol 2011; 9: 524-30.e1; quiz e60.
  13. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethinicity. Hepatology 2004; 40: 1387-95.
    Pubmed CrossRef
  14. Omagari K, Kadokawa Y, Masuda J, Egawa I, Sawa T, Hazama H, et al. Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics. J Gastroenterol Hepatol 2002; 17: 1098-105.
    Pubmed CrossRef
  15. Lovejoy JC, Champagne CM, de Jonge L, Xie H, Smith SR. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes (Lond) 2008; 32: 949-58.
    Pubmed KoreaMed CrossRef
  16. Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002; 122: 1649-57.
    Pubmed CrossRef
  17. Morrell A, Tallino S, Yu L, Burkhead JL. The role of insufficient copper in lipid synthesis and fatty-liver disease. IUBMB Life 2017; 69: 263-70.
    Pubmed KoreaMed CrossRef
  18. Danks DM. Copper deficiency in humans. Annu Rev Nutr 1988; 8: 235-57.
    Pubmed CrossRef
  19. Klevay LM. Alzheimer’s disease as copper deficiency. Med Hypotheses 2008;70: 802-7.
    Pubmed CrossRef
  20. Tallino S, Duffy M, Ralle M, Cortés MP, Latorre M, Burkhead JL. Nutrigenomics analysis reveals that copper deficiency and dietary sucrose up-regulate inflammation, fibrosis and lipogenic pathways in a mature rat model of nonalcoholic fatty liver disease. J Nutr Biochem 2015; 26: 996-1006.
    Pubmed KoreaMed CrossRef
  21. Chouinard-Watkins R, Plourde M. Fatty acid metabolism in carriers of apolipoprotein E epsilon 4 allele: is it contributing to higher risk of cognitive decline and coronary heart disease? Nutrients 2014; 6: 4452-71.
    Pubmed KoreaMed CrossRef
  22. Huang Y, Mahley RW. Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases. Neurobiol Dis 2014; 72 Pt A: 3-12.
  23. Aigner E, Strasser M, Haufe H, Sonnweber T, Hohla F, Stadlmayr A, et al. A role for low hepatic copper concentrations in nonalcoholic fatty liver disease. Am J Gastroenterol 2010; 105: 1978-85.
    Pubmed CrossRef
  24. Stättermayer AF, Traussnigg S, Aigner E, Kienbacher C, Huber-Schönauer U, Steindl-Munda P, et al. Low hepatic copper content and PNPLA3 polymorphism in non-alcoholic fatty liver disease in patients without metabolic syndrome. J Trace Elem Med Biol 2017; 39: 100-7.
    Pubmed CrossRef
  25. DiSilvestro RA. Zinc in relation to diabetes and oxidative disease. J Nutr 2000; 130(5S Suppl): 1509-11S.
  26. Lee EJ, Kim SM. The association of hair zinc with metabolic risk factors for selected women in Korea. Korean J Obes 2005; 14: 170-7.
  27. Guo CH, Chen PC, Ko WS. Status of essential trace minerals and oxidative stress in viral hepatitis C patients with nonalcoholic fatty liver disease. Int J Med Sci 2013; 10: 730-7.
    Pubmed KoreaMed CrossRef
  28. Jackson MJ. Physiology of zinc: general aspects. In: Mills CF, editor. Zinc in human biology. London: Springer-Verlag; 1989. p. 1-14.
    KoreaMed CrossRef
  29. Hilderbrand DC, White DH. Trace-element analysis in hair: an evaluation. Clin Chem 1974; 20: 148-51.

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