Skip to main content
SpringerLink
Log in

The Alteration of Zinc Transporter Gene Expression Is Associated with Inflammatory Markers in Obese Women

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

An Erratum to this article was published on 06 June 2014

Abstract

Obesity, a chronic inflammatory state, is associated with altered zinc metabolism. ZnT and Zip transporters are involved in the regulation of zinc metabolism. This study examined the relationships among obesity, zinc transporter gene expression, and inflammatory markers in young Korean women. The messenger RNA (mRNA) levels of leukocyte zinc transporters between obese (BMI = 28.3 ± 0.5 kg/m2, n = 35) and nonobese (BMI = 20.7 ± 0.2 kg/m2, n = 20) women aged 18–28 years were examined using quantitative real-time polymerase chain reaction. Inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6, were measured in serum by enzyme immunoassay. ZnT1 and Zip1 were the most abundantly expressed zinc transporters in leukocytes. The mRNA levels of many zinc transporters (ZnT4, ZnT5, ZnT9, Zip1, Zip4, and Zip6) were significantly lower in obese women, and expression of these genes was inversely correlated with BMI and body fat percentage. In addition, inflammatory markers (CRP and TNF-α) were significantly higher in obese women. The mRNA levels of ZnT4, Zip1, and Zip6 were inversely correlated with CRP (P < 0.05), and mRNA levels of ZnT4 and ZnT5 were inversely correlated with TNF-α (P < 0.05). In standardized simple regression models, levels of TNF-α and CRP were negatively associated with mRNA levels of zinc transporters such as ZnT4, ZnT5, Zip1, and Zip6 (P < 0.05). These results suggest that the expression of zinc transporters may be altered in obese individuals. Changes in zinc transporters may also be related to the inflammatory state associated with obesity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Reference

  1. Caballero B (2007) The global epidemic of obesity: an overview. Epidemiol Rev 29:1–5

    Article  PubMed  Google Scholar 

  2. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17(1):4–12

    CAS  PubMed  Google Scholar 

  3. Marreiro DN, Geloneze B, Tambascia MA, Lerario AC, Halpern A, Cozzolino SM (2006) Effect of zinc supplementation on serum leptin levels and insulin resistance of obese women. Biol Trace Elem Res 112(2):109–118

    Article  CAS  PubMed  Google Scholar 

  4. Tungtrongchitr R, Pongpaew P, Phonrat B, Tungtrongchitr A, Viroonudomphol D, Vudhivai N, Schelp FP (2003) Serum copper, zinc, ceruloplasmin and superoxide dismutase in Thai overweight and obese. J Med Assoc Thai 86(6):543–551

    PubMed  Google Scholar 

  5. Ennes Dourado Ferro F, de Sousa Lima VB, Mello Soares NR, Franciscato Cozzolino SM, do Nascimento Marreiro D (2011) Biomarkers of metabolic syndrome and its relationship with the zinc nutritional status in obese women. Nutr Hosp 26(3):650–654

    CAS  PubMed  Google Scholar 

  6. Begin-Heick N, Dalpe-Scott M, Rowe J, Heick HM (1985) Zinc supplementation attenuates insulin secretory activity in pancreatic islets of the ob/ob mouse. Diabetes 34(2):179–184

    Article  CAS  PubMed  Google Scholar 

  7. Foster M, Samman S (2012) Zinc and regulation of inflammatory cytokines: implications for cardiometabolic disease. Nutrients 4(7):676–694

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Garcia OP, Ronquillo D, Caamano Mdel C, Camacho M, Long KZ, Rosado JL (2012) Zinc, vitamin A, and vitamin C status are associated with leptin concentrations and obesity in Mexican women: results from a cross-sectional study. Nutr Metab (Lond) 9(1):59

    Article  CAS  Google Scholar 

  9. Freire SC, Fisberg M, Cozzolino SM (2013) Dietary intervention causes redistribution of zinc in obese adolescents. Biol Trace Elem Res 154(2):168–177

    Article  CAS  PubMed  Google Scholar 

  10. Lichten LA, Cousins RJ (2009) Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev Nutr 29:153–176

    Article  PubMed  Google Scholar 

  11. Andree KB, Kim J, Kirschke CP, Gregg JP, Paik H, Joung H, Woodhouse L, King JC, Huang L (2004) Investigation of lymphocyte gene expression for use as biomarkers for zinc status in humans. J Nutr 134(7):1716–1723

    CAS  PubMed  Google Scholar 

  12. Overbeck S, Uciechowski P, Ackland ML, Ford D, Rink L (2008) Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9. J Leukoc Biol 83(2):368–380

    Article  CAS  PubMed  Google Scholar 

  13. Aydemir TB, Blanchard RK, Cousins RJ (2006) Zinc supplementation of young men alters metallothionein, zinc transporter, and cytokine gene expression in leukocyte populations. Proc Natl Acad Sci U S A 103(6):1699–1704

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Smidt K, Pedersen SB, Brock B, Schmitz O, Fisker S, Bendix J, Wogensen L, Rungby J (2007) Zinc-transporter genes in human visceral and subcutaneous adipocytes: lean versus obese. Mol Cell Endocrinol 264(1–2):68–73

    Article  CAS  PubMed  Google Scholar 

  15. World Health Organization (WHO) (2000) The Asia Pacific perspective: redefining obesity and its treatment

  16. World Health Organization (WHO) (2008) Waist circumference and waist-hip ratio: report of a WHO expert consultation

  17. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW, Kurtz T, Sheps SG, Roccella EJ (2005) Recommendations for blood pressure measurement in humans and experimental animals: Part 1. Blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension 45(1):142–161

    Article  CAS  PubMed  Google Scholar 

  18. Kim J, Paik HY, Joung H, Woodhouse LR, Li S, King JC (2004) Zinc supplementation reduces fractional zinc absorption in young and elderly korean women. J Am Coll Nutr 23(4):309–315

    Article  CAS  PubMed  Google Scholar 

  19. Jacobs RM, Lumsden JH, Taylor JA, Grift E (1991) Effects of interferents on the kinetic Jaffe reaction and an enzymatic colorimetric test for serum creatinine concentration determination in cats, cows, dogs and horses. Can J Vet Res 55(2):150–154

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Koenig W, Lowel H, Baumert J, Meisinger C (2004) C-reactive protein modulates risk prediction based on the Framingham score: implications for future risk assessment: results from a large cohort study in southern Germany. Circulation 109(11):1349–1353

    Article  PubMed  Google Scholar 

  21. Idriss HT, Naismith JH (2000) TNF alpha and the TNF receptor superfamily: structure–function relationship(s). Microsc Res Tech 50(3):184–195

    Article  CAS  PubMed  Google Scholar 

  22. Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T, Kishimoto T (1993) IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science 260(5115):1808–1810

    Article  CAS  PubMed  Google Scholar 

  23. Ozata M, Mergen M, Oktenli C, Aydin A, Sanisoglu SY, Bolu E, Yilmaz MI, Sayal A, Isimer A, Ozdemir IC (2002) Increased oxidative stress and hypozincemia in male obesity. Clin Biochem 35(8):627–631

    Article  CAS  PubMed  Google Scholar 

  24. Marreiro DN, Fisberg M, Cozzolino SM (2004) Zinc nutritional status and its relationships with hyperinsulinemia in obese children and adolescents. Biol Trace Elem Res 100(2):137–149

    Article  PubMed  Google Scholar 

  25. Marotta A, Todisco N, Di Toro A, Toraldo R, Ponte G, Perrone L (1995) Zinc content of lymphomonocytes in obese children. Nutr Res 15(10):1411–1415

    Article  CAS  Google Scholar 

  26. Huang L, Yu YY, Kirschke CP, Gertz ER, Lloyd KK (2007) Znt7 (Slc30a7)-deficient mice display reduced body zinc status and body fat accumulation. J Biol Chem 282(51):37053–37063

    Article  CAS  PubMed  Google Scholar 

  27. Lang C, Murgia C, Leong M, Tan LW, Perozzi G, Knight D, Ruffin R, Zalewski P (2007) Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. Am J Physiol Lung Cell Mol Physiol 292(2):L577–L584

    Article  CAS  PubMed  Google Scholar 

  28. Palmiter RD, Huang L (2004) Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers. Pflugers Arch 447(5):744–751

    Article  CAS  PubMed  Google Scholar 

  29. Lee DY, Shay NF, Cousins RJ (1992) Altered zinc metabolism occurs in murine lethal milk syndrome. J Nutr 122(11):2233–2238

    CAS  PubMed  Google Scholar 

  30. Murgia C, Vespignani I, Rami R, Perozzi G (2006) The Znt4 mutation inlethal milk mice affects intestinal zinc homeostasis through the expression of other Zn transporters. Genes Nutr 1(1):61–70

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Cassel GH (1978) Zinc: a review of current trends in therapy and our knowledge of its toxicity. Del Med J 50(6):323–328

    CAS  PubMed  Google Scholar 

  32. Kelishadi R, Hashemipour M, Adeli K, Tavakoli N, Movahedian-Attar A, Shapouri J, Poursafa P, Rouzbahani A (2010) Effect of zinc supplementation on markers of insulin resistance, oxidative stress, and inflammation among prepubescent children with metabolic syndrome. Metab Syndr Relat Disord 8(6):505–510

    Article  CAS  PubMed  Google Scholar 

  33. Huang L, Kirschke CP, Zhang Y, Yu YY (2005) The ZIP7 gene (Slc39a7) encodes a zinc transporter involved in zinc homeostasis of the Golgi apparatus. J Biol Chem 280(15):15456–15463

    Article  CAS  PubMed  Google Scholar 

  34. Kitamura H, Morikawa H, Kamon H, Iguchi M, Hojyo S, Fukada T, Yamashita S, Kaisho T, Akira S, Murakami M, Hirano T (2006) Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. Nat Immunol 7(9):971–977

    Article  CAS  PubMed  Google Scholar 

  35. Kim J (2013) Dietary zinc intake is inversely associated with systolic blood pressure in young obese women. Nutr Res Pract 7(5):380–384

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Cousins RJ, Liuzzi JP, Lichten LA (2006) Mammalian zinc transport, trafficking, and signals. J Biol Chem 281(34):24085–24089

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) founded by the Ministry of Education, Science, and Technology (NRF-2010-0011226 to J.C. and NRF2012R1A1A1012317 to J.K.).

Author information

Authors and Affiliations

  1. Deptartment of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, 151-742, South Korea

    Hwayoung Noh & Hee Young Paik

  2. Deparment of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, 1732 Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 446-701, South Korea

    Jihye Kim

  3. Research Institute of Medical Nutrition, Kyung Hee University, Seoul, 130-701, South Korea

    Jihye Kim

  4. Deptartment of Food and Nutrition, College of Human Ecology, Kyung Hee University, 26 Kyunghee-daero Dongdaemun-gu, Seoul, 130-701, South Korea

    Jayong Chung

Authors
  1. Hwayoung Noh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hee Young Paik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jihye Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jayong Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jihye Kim or Jayong Chung.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Noh, H., Paik, H.Y., Kim, J. et al. The Alteration of Zinc Transporter Gene Expression Is Associated with Inflammatory Markers in Obese Women. Biol Trace Elem Res 158, 1–8 (2014). https://doi.org/10.1007/s12011-014-9902-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-9902-1

Keywords

Search

Navigation