Skip to main content
SpringerLink
Log in

Zinc Transporter ZnT1 mRNA Expression Is Negatively Associated with Leptin Serum Concentrations but Is not Associated with Insulin Resistance or Inflammatory Markers in Visceral Adipose Tissue

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

Abstract

The aim of this study was to evaluate the relationship between biomarkers of chronic inflammation, insulin resistance, and zinc transporter ZnT1 expression in human visceral adipose tissue. Visceral adipose tissue obtained from 47 adults undergoing laparoscopic surgery for cholecystectomy was used to analyze ZnT1 mRNA expression by RT-qPCR. ZnT1 mRNA levels were compared between subjects with normal weight, overweight, and obesity. A significantly lower ZnT1 expression was observed in overweight and obesity compared with normal-weight subjects (p = 0.0016). Moreover, subjects with normal weight had significantly higher serum zinc concentration (97.7 ± 13.1 mg/L) than subjects with overweight (87.0 ± 12.8 mg/L) and obesity (83.1 ± 6.6 mg/L) (p = 0.002). Pearson test showed a positive correlation between serum zinc concentrations and ZnT1 mRNA expression in visceral adipose tissue (r = 0.323; p = 0.031) and a negative correlation with body mass index (r =  − 0.358; p = 0.013). A linear regression model was used to analyze the associations between ZnT1 mRNA expression and serum zinc levels, insulin resistance (HOMA2-IR), serum adipokines (leptin and adiponectin), and serum inflammation biomarkers (tumor necrosis factor alpha, interleukin-6, and C-reactive protein). Interestingly, leptin concentrations were negatively associated with ZnT1 mRNA expression (p = 0.012); however, no significant associations were found for the rest of the analyzed variables. Future research is needed to analyze the causality of negative association between ZntT1 expression in visceral adipose tissue and leptin.

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
Fig. 2

Similar content being viewed by others

Data Availability

The datasets generated during the current study are available from the corresponding author upon reasonable request.

References

  1. WHO Consultation on Obesity (1999: Ginebra, Suiza); y Organización Mundial de la Salud. (2000) Obesity: preventing and managing the global epidemic: report of a WHO consultation. Organización Mundial de la Salud. https://apps.who.int/iris/handle/10665/42330 Accessed 21 June 2021.

  2. Scherer T, Lindtner C, Zielinski E, O’hare J, Filatova N, Buettner C (2012) Short term voluntary overfeeding disrupts brain insulin control of adipose tissue lipolysis. J Biol Chem. https://doi.org/10.1074/jbc.M111.307348

    Article  PubMed  PubMed Central  Google Scholar 

  3. Shibata R, Ouchi N, Ohashi K, Murohara T (2017) The role of adipokines in cardiovascular disease. J Cardiol. https://doi.org/10.1016/j.jjcc.2017.02.006

  4. Calder PC, Albers R, Antoine JM (2009) Inflammatory disease processes and interactions with nutrition. Br J Nutr. https://doi.org/10.1017/S0007114509377867

    Article  PubMed  Google Scholar 

  5. Troche C, Aydeir T, Cousins R (2016) Zinc transporter Slc39a14 regulates inflammatory signaling associated with hypertrophic adiposity. Am J Physiol Endocrinol Metab. https://doi.org/10.1152/ajpendo.00421.2015

    Article  PubMed  Google Scholar 

  6. Zavala G, Long KZ, Garcia OP, Caamano Mdel C, Aguilar T, Salgado LM, Rosado JL (2013) Specific micronutrient concentrations are associated with inflammatory cytokines in a rural population of Mexican women with a high prevalence of obesity. Br J Nutr. https://doi.org/10.1017/S0007114512001912

    Article  PubMed  Google Scholar 

  7. Garcia OP, Ronquillo D, Caamaño MD, Camacho M, Long KZ, Rosado JL (2013) 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. https://doi.org/10.3390/nu5125012

    Article  Google Scholar 

  8. Seham F, Safaa H, Wafaa F, Mona A, Laila M, Asmaa M (2014) Serum trace elements in obese Egyptian children: a case-control study. Ital J Pediatr. https://doi.org/10.1186/1824-7288-40-20

    Article  Google Scholar 

  9. Suliburska J, Cofta S, Gajewska E, Kalmus G, Sobieska M, Samborski W et al (2013) The evaluation of selected serum mineral concentrations and their association with insulin resistance in obese adolescents. Eur Rev Med Pharmacol Sci 17:2396–2400

    CAS  PubMed  Google Scholar 

  10. Rios-Lugo MJ, Madrigal-Arellano C, Gaytán-Hernández D, Hernández-Mendoza H, Romero-Guzmán ET (2020) Association of serum zinc levels in overweight and obesity. Biol Trace Elem Res. https://doi.org/10.1007/s12011-020-02060-8

    Article  PubMed  Google Scholar 

  11. Kambe T, Tsuji T, Hashimoto A, Itsumuia N (2015) The physiological, biochemical and molecular roles of zinc transporters and zinc homeostasis and metabolism. Physiol Rev. https://doi.org/10.1152/physrev.00035.2014

    Article  PubMed  Google Scholar 

  12. Jarosz M, Olbert M, Wyszogrodzka G, Młyniec K, Librowski T (2017) Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling. Inflammopharmacology. https://doi.org/10.1007/s10787-017-0309-4

    Article  PubMed  PubMed Central  Google Scholar 

  13. Prassad AS (2009) Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care. https://doi.org/10.1097/MCO.0b013e3283312956

    Article  Google Scholar 

  14. Lichten L, y Cousins R (2009) Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev Nutr. https://doi.org/10.1146/annurev.nutr.24.012003.132402

    Article  PubMed  Google Scholar 

  15. Kimura T, Kambe T (2016) The functions of metallothionein and ZIP and ZnT transporters: an overview and perspective. Int J Mol Sci. https://doi.org/10.3390/ijms17030336

    Article  PubMed  PubMed Central  Google Scholar 

  16. Liuzzi J, Lichten L, Rivera S, Blanchard R, Aydemir T, Knutson M (2005) Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.0502257102

    Article  PubMed  PubMed Central  Google Scholar 

  17. Hosseini R, Ferns GA, Sahebkar A, Mirshekar MA, Jalali M (2021) Zinc supplementation is associated with a reduction in serum markers of inflammation and oxidative stress in adults: a systematic review and meta-analysis of randomized controlled trials. Cytokine. https://doi.org/10.1016/j.cyto.2020.155396

    Article  PubMed  Google Scholar 

  18. Smidt K, Pedersen SB, Brock B, Schmitz O, Fiskers S, Bendix J, Wogensen L, Rungby J (2007) Zinc transporter genes in human visceral and subcutaneous adipocytes: lean versus obese. Mol Cell Endocrinol. https://doi.org/10.1016/j.mce.2006.10.010

    Article  PubMed  Google Scholar 

  19. L Mota Martins ARS Oliveira de KJC Cruz CJB Araujo de FE Oliveira de D Marreiro GS Sousa de NNB Nogueira do 2014 Influence of cortisol on zinc metabolism in morbidly obese women NutrHosp https://doi.org/10.3305/nh.2014.29.1.6890

  20. Morais JBS, Severo JS, Beserra JB, de Oiveira ARS, Cruz KJC, de Sousa Melo SR et al (2019) Association between cortisol, insulin resistance and zinc in obesity: a mini-review. Biol Trace Elem Res. https://doi.org/10.1007/s12011-018-1629-y

    Article  PubMed  Google Scholar 

  21. Egefjord L, Jensen JL, Bang-Berthelsen CH, Petersen AB, Smidt K, Schmitz O et al (2009) Zinc transporter gene expression is regulated by pro-inflammatory cytokines: a potential role for zinc transporters in beta-cell apoptosis? BMC Endocr Disord. https://doi.org/10.1186/1472-6823-9-7

    Article  PubMed  PubMed Central  Google Scholar 

  22. Declaration of Helsinki of the World Medical Association (2001) Ethical principles for medical research in human beings. Ann Fac Med. https://doi.org/10.1001/jama.2013.281053

    Article  Google Scholar 

  23. Mexican Association of Market and Opinion Intelligence Agencies (AMAI) to measure the socioeconomic level. 2018. Available from: https://www.amai.org/NSE Accessed 21 June 2021.

  24. Craig C, Marshall A, Sjostrom M, Bauman AE, Booth ML, Pratt M (2003) International physical activity questionnaire: 12- country reliability and validity. Med Sci Sports Exercise. https://doi.org/10.1249/01.MSS.0000078924.61453.FB

    Article  Google Scholar 

  25. Lohman T, Roche A, Martorell R (1998) Anthropometric Standardization Reference Manual. Human Kinetics, Champaign, IL. https://doi.org/10.1002/ajhb.1310040323

    Book  Google Scholar 

  26. World Health Organization, “Obesity and overweight,” 2022. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight Accessed 21 June 2021

  27. Ascaso JF, Pardo S, Real JT, Lorente RI, Priego A, Carmena R. Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care. https://doi.org/10.2337/diacare.26.12.3320

  28. Hotz C, Peerson J, Brown K (2003) Suggested lower cutoffs of serum zinc concentrations for assessing zinc status: reanalysis of the second National Health and Nutrition Examination Survey data (1976–1980). Am J Clin Nutr. https://doi.org/10.1093/ajcn/78.4.756

    Article  PubMed  Google Scholar 

  29. American Diabetes Association https://diabetes.org/diabetes/a1c/diagnosis. Accessed 11 november 2020.

  30. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation. https://doi.org/10.1161/circ.106.25.3143

  31. Liu MJ, Bao S, Bolin ER, Burris DL, Xu X, Sun Q, Killilea DW, Shen Q, Ziouzenkova O, Belury MA, Failla ML, Knoell DL (2013) Zinc deficiency augments leptin production and exacerbates macrophage infiltration into adipose tissue in mice fed a high-fat diet. J Nutr. https://doi.org/10.3945/jn.113.175158

    Article  PubMed  PubMed Central  Google Scholar 

  32. Reis B, dos Santos VD, da Costa MD, da Góes DS, Mendes-Netto R, Cozzolino S (2020) Zinc nutritional status influences ZnT1 and ZIP4 gene expression in children with a high risk of zinc deficiency. J Trace Elem Med Biol. https://doi.org/10.1016/j.jtemb.2020.126537

    Article  PubMed  Google Scholar 

  33. McMahon RJ, Cousins RJ (1998) Regulation of the zinc transporter ZnT-1 by dietary zinc. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.95.9.4841

    Article  PubMed  PubMed Central  Google Scholar 

  34. Langmade SJ, Ravindra R, Daniels PJ, Andrews GK (2000) The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene. J Biol Chem. https://doi.org/10.1074/jbc.m007339200

    Article  PubMed  Google Scholar 

  35. Palmiter RD (2004) Protection against zinc toxicity by metallothionein and zinc transporter 1. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.0401022101

    Article  PubMed  PubMed Central  Google Scholar 

  36. Enriori PJ, Evans AE, Sinnayah P, Cowley MA (2006) Leptin resistance and obesity. Obesity (Silver Spring). https://doi.org/10.1038/oby.2006.319

    Article  PubMed  Google Scholar 

  37. Do M, Nam S, Hong S, Kim W, Duncan J, Beattie J, Trayhurn P (2002) Metallothionein gene expresión in human adipose tissue from lean and obese subjects. Horm Metab Res. https://doi.org/10.1055/s-2002-33254

    Article  PubMed  Google Scholar 

  38. Trayhurn P, Duncan J, Wood A, Beattie J (2000) Metallothionein gene expression and secretion in white adipose tissue. Am J Physiol regul Integr Comp Phhysiol. https://doi.org/10.1152/ajpregu.2000.279.6.r2329

    Article  Google Scholar 

  39. Wang B, Wood S, Trayhurn P (2008) PCR arrays identify metallothionein-3 as a highly hypoxia- inducible gene in human adipocytes. Biochem Boiphys Res Commun. https://doi.org/10.1016/j.bbrc.2008.01.036

    Article  Google Scholar 

  40. Nishito Y, Kambe T (2019) Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately controlled by cellular zinc levels. J Biol Chem. https://doi.org/10.1074/jbc.ra119.010227

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wijesekara N, Dai FF, Hardy AB, Giglou PR, Bhattacharjee A, Koshkin V et al (2010) Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia. https://doi.org/10.1007/s00125-010-1733-9

    Article  PubMed  PubMed Central  Google Scholar 

  42. Wang X, Gao H, Wu W, Xie E, Yu Y, He X, Li J, Zheng W, Wang X, Cao X, Meng Z, Chen L, Min J, Wang F (2019) The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic beta-cells via Sirt1- and Pgc-1alpha-mediated regulation of Glut2. Protein Cell. https://doi.org/10.1007/s13238-018-0580-1

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tepaamorndech S, Kirschke CP, Pedersen TL, Keyes WR, Newman JW, Huang L (2016) Zinc transporter 7 deficiency affects lipid synthesis in adipocytes by inhibiting insulin-dependent Akt activation and glucose uptake. FEBS J. https://doi.org/10.1111/febs.13582

    Article  PubMed  Google Scholar 

  44. Fukunaka A, Fukada T, Bhin J, Suzuki L, Tsuzuki T, Takamine Y et al (2017) Zinc transporter ZIP13 suppresses beige adipocyte biogenesis and energy expenditure by regulating C/EBP-beta expression. PLoS Genet. https://doi.org/10.1371/journal.pgen.1006950

    Article  PubMed  PubMed Central  Google Scholar 

  45. Prasad AS (2014) Zinc: an antioxidant and anti-inflammatory agent: role of zinc in degenerative disorders of aging. J Trace Elem Med Biol. https://doi.org/10.1016/j.jtemb.2014.07.019

    Article  PubMed  Google Scholar 

  46. Hennigar SR, McClung JP (2016) Hepcidin attenuates zinc efflux in Caco-2 cells. J Nutr. https://doi.org/10.3945/jn.116.237081

    Article  PubMed  Google Scholar 

  47. Stoffel NU, El-Mallah C, Herter-Aeberli I et al (2020) The effect of central obesity on inflammation, hepcidin, and iron metabolism in young women. Int J Obes. https://doi.org/10.1038/s41366-020-0522-x

    Article  Google Scholar 

  48. Moore Heslin A, O’Donnell A, Buffini M, Nugent AP, Walton J, Flynn A, McNulty BA (2021) Risk of iron overload in obesity and implications in metabolic health. Nutrients. https://doi.org/10.3390/nu13051539

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the Department of Surgery of the Hospital General de Querétaro as well as the Secretaria de Salud del Estado de Querétaro, specially to Dr. Ivette Mata Maqueda. The authors are also grateful to Sheini Ruturi Sánchez for her technical assistance. AKTA, PEI, and FCM were supported by graduate fellowships from CONAHCYT, 552847, 516954, and 62531, respectively.

Funding

This work was supported by the Sociedad Mexicana de Nutrición y Endocrinología, AC (SMNE 2018), and the Universidad Autónoma de Querétaro (FOPER-2020-FME01894).

Author information

Authors and Affiliations

  1. Endocrinology and Nutrition Laboratory, Center of Advanced Biomedical Research, School of Medicine, Autonomous University of Queretaro, Carretera a Chichimequillas S/N Ejido Bolaños Av. Universidad Dirección a La Derecha, 76140, Santiago de Querétaro, Qro., Mexico

    Ana Karen Torres-Arreola, Paulina Estrella-Ibarra, Francisco Campos-Maldonado, Adriana Jheny Rodriguez-Méndez, Juan Carlos Solís-Sáinz & Pablo García-Solís

  2. Biomedical Sciences PhD Program, School of Medicine, Autonomous University of Queretaro, Queretaro, Mexico

    Ana Karen Torres-Arreola & Francisco Campos-Maldonado

  3. Department of Human Nutrition, School of Natural Sciences, Autonomous University of Queretaro, Queretaro, Mexico

    Olga P. García & Mariela Camacho-Barron

  4. Biological Sciences PhD Program, School of Natural Sciences, Autonomous University of Queretaro, Queretaro, Mexico

    Paulina Estrella-Ibarra

  5. Department of General Surgery, General Hospital of Queretaro, Queretaro, Mexico

    María del Carmen Aburto-Fernández & Ricardo Martín Lerma-Alvarado

Authors
  1. Ana Karen Torres-Arreola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olga P. García
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paulina Estrella-Ibarra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francisco Campos-Maldonado
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mariela Camacho-Barron
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. María del Carmen Aburto-Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ricardo Martín Lerma-Alvarado
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Adriana Jheny Rodriguez-Méndez
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Juan Carlos Solís-Sáinz
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pablo García-Solís
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AKT: conceptualization, methodology, formal analysis, visualization, investigation, and writing—original draft; OPG: conceptualization, methodology, formal analysis, resources, investigation, and writing—review and editing; PEI: validation, methodology, investigation, and writing—review and editing; FCM: validation, investigation, and writing—review and editing; MCB: validation, investigation, and writing—review and editing; MCAF: investigation and writing—review and editing; RMLA: investigation and writing—review and editing; AJRM: resources, investigation, and writing—review and editing; JCSS: visualization and writing—review and editing; and PGS: conceptualization, formal analysis, visualization, writing—review and editing, supervision, project administration, and funding acquisition.

Corresponding author

Correspondence to Pablo García-Solís.

Ethics declarations

Ethics Approval

The study was conducted according to the Declaration of Helsinki guidelines [21], and the protocol was approved by the Bioethics Committee of the School of Medicine of the Autonomous University of Querétaro (Registration number 01–09711/2017).

Consent to Participate

Informed consent was obtained from all individual participants included in the study.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Torres-Arreola, A.K., García, O.P., Estrella-Ibarra, P. et al. Zinc Transporter ZnT1 mRNA Expression Is Negatively Associated with Leptin Serum Concentrations but Is not Associated with Insulin Resistance or Inflammatory Markers in Visceral Adipose Tissue. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-024-04089-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12011-024-04089-5

Keywords

Search

Navigation