Biological Trace Element Research

, Volume 112, Issue 2, pp 109–118 | Cite as

Effect of zinc supplementation on serum leptin levels and insulin resistance of obese women

  • Dilina do Nascimento Marreiro
  • Bruno Geloneze
  • Marcos A. Tambascia
  • Antonio C. Lerário
  • Alfredo Halpern
  • Silvia Maria Franciscato Cozzolino


Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc might play an important role in appetite regulation and its administration stimulates leptin production. However, there are few reports in the literature on its role on leptin levels in the obese population. The present work asseses the effect of zinc supplementation on serum leptin levels in insulin resistance (IR). A prospective double-blind, randomized, clinical, placebo-controlled study was conducted. Fifty-six normal glucose-tolerant obese women (age: 25–45 yr, body mass index [BMI]=36.2 ±2.3 kg/m2) were randomized for treatment with 30 mg zinc daily for 4 wk. Baseline values of both groups were similar for age, BMI, caloric intake, insulin concentration, insulin resistance, and zinc concentration in diet, plasma, urine, and erythrocytes. Insulin and leptin were measured by radioimmunoassay and IR was estimated by the homeostasis model assessment (HOMA). The determinations of zinc in plasma, erythrocytes, and 24-h urine were performed by using atomic absorption spectrophotometry. After 4 wk, BMI, fasting glucose, and zinc concentration in plasma and erythrocyte did not change in either group, although zinc concentration in the urine increased from 385.9±259.3 to 470.2±241.2±μg/24 h in the group with zinc supplementation (p<0.05). Insulin did not change in the placebo group, whereas there was a significant decrease of this hormone in the supplemented group. HOMA also decreased from 5.8±2.6 to 4.3±1.7 (p<0.05) in the zinc-supplemented group but did not change in the placebo group. Leptin did not change in the placebo group. In the zinc group, leptin was 23.6±12.3 μg/L and did not change. More human data from a unique population of obese individuals with documented insulin resistance would be useful in guiding future studies on zinc supplementation (with higher doses or longer intervals) or different measures.

Index Entries

Zinc leptin obesity insulin resistance metabolism 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    G. M. Reaven and A. Laws, Insulin resistance, compensatory hyperinsulinemia, and coronary heart disease, Diabetologia 37, 948–952 (1994).PubMedGoogle Scholar
  2. 2.
    J. P. Despres, B. Lamarche, and P. Mauriege, Hyperinsulinemia as an independent risk factor for ischemic heart disease. N. Engl. J. Med. 334, 952–957 (1996).PubMedCrossRefGoogle Scholar
  3. 3.
    A. O. MacDougald, C. S. Hwang, H. Fan, and M. D. Lane, Regulated expression of the obese product (leptin) in white adipose tissue and 3T3-L1 adipocytes. Proc. Natl. Acad. Sci. USA 92, 9034–9037 (1995).PubMedCrossRefGoogle Scholar
  4. 4.
    J. Rentsch and M. Chiesi, Regulation of ob gene mRNA levels in cultured adipocytes, FEBS Lett. 379, 55–59 (1996).PubMedCrossRefGoogle Scholar
  5. 5.
    J. I. Halaas, K. S. Gajiwala, and M. Maffei, Weight-reducing effects of the plasma protein encoded by the obese gene, Science 269, 543–546 (1995).PubMedCrossRefGoogle Scholar
  6. 6.
    T. W. Stephens, M. Basinski, and P. K. Bristow, The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature 377, 530–532 (1995).PubMedCrossRefGoogle Scholar
  7. 7.
    R. V. Considine, M. K. Sinha, and M. L. Heiman, Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334, 292–295 (1996).PubMedCrossRefGoogle Scholar
  8. 8.
    B. S. Hamilton, D. Paglia, A. Y. M. Kwan, and M. Deitel, Increased obese nRNA expression in omental fat cells from massively obese humans. Nature Med. 1, 953–956 (1995).PubMedCrossRefGoogle Scholar
  9. 9.
    S. M. Haffner, H. Miettinen, L. Mykkanen, D. L. Rainwater, and M. Laakso, Leptin concentrations and insulin sensitivity in normoglycemic men. Int. J. Related Metab. Disord. 21, 393–399 (1997).CrossRefGoogle Scholar
  10. 10.
    M. D. Chen, P. Lin, and W. Sheu, Zinc status in plasma of obese individuals during glucose administration, Biol. Trace Element Res. 60, 123–129 (1997).Google Scholar
  11. 11.
    G. Martino, M. G. Matera, B. Martino, C. Vacca, S. Martino, and F. Rossi, Relationship between zinc and obesity, J. Med. 24, 177–183 (1993).PubMedGoogle Scholar
  12. 12.
    L. Perrone, G. Gialanella, R. Moro, et al., Zinc, copper, and iron in obese children and adolescents. Nutr. Res. 18, 183–189 (1998).CrossRefGoogle Scholar
  13. 13.
    C. S. Mantzoros, A. S. Prasad, F. W. J. Beck, et al., Zinc may regulate serum leptin concentrations in humans, J. Am. Coll. Nutr, 17, 270–275 (1998).PubMedGoogle Scholar
  14. 14.
    L. Coulston and P. Dandona, Insulin-like effects of zinc on adipocytes, Diabetes 29, 665–667 (1980).PubMedGoogle Scholar
  15. 15.
    Biodynamics, Monitor de composição corporal: biodynamics modelo 310, Biodynamics, (1995).Google Scholar
  16. 16.
    R. C. Whitehouse, A. S. Prasad, P. I. Rabbani, and Z. T. Cossack, Zinc in plasma, neutrophils lymphocytes, and erythrocytes as determined by flameless atomic absorption spectrophotometry, Clin. Chem. 28, 475–480 (1982).PubMedGoogle Scholar
  17. 17.
    M. P. Rodriguez, A. Narizano, V. Demczylo, and A. Cid, A simpler method for the determination of zinc human plasma levels by flame atomic absorption spectrophotometry, Atomic Spectrosc. 10, 68–70 (1989).Google Scholar
  18. 18.
    O. W. Van Assendelft. The measurement of hemoglobin, in Modern Concepts in Hematology, G. Izak and S. M. Lewis (eds.), Academic, New York, pp. 4–25 (1972).Google Scholar
  19. 19.
    S. Kilerich, M. S. Christiansen, and J. Naestoft. Determination of zinc in serum and urine by atomic absorption spectrophotometry; relationship between serum levels of zinc and proteins in 104 normal subjects. Clin. Chim. Acta 105, 231–239 (1980).CrossRefGoogle Scholar
  20. 20.
    D. R. Matthews, J. P. Hosker, A. S. Rudenski, B. A. Naylor, D. F. Treacher, and R. C. Turner, Homeostasis Model Assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419 (1985).PubMedCrossRefGoogle Scholar
  21. 21.
    J. C. King and C. L. Keen, Zinc, in Modern Nutrition in Health and Disease, 8th ed., M. E. Shils, J. A. Olson, and M. Shike, eds., Lea and Febiger, Philadelphia, pp. 214–230 (1994).Google Scholar
  22. 22.
    D. L. Donaldson, C. C. Smith, and M. S. Walker, Tissue zinc and copper levels in diabetic C57BL/KsJ (ob/ob) mice fed a zinc-deficient diet: lack of evidence for specific depletion of tissue zinc stores. J. Nutr. 118, 1502–1508 (1988).PubMedGoogle Scholar
  23. 23.
    N. Begin-heick, M. Dalpe-Scott, J. Rowe, and H. M. C. Heick, Zinc supplementation attenuates secretory activity in pancreatic islets of the ob/ob mouse, Diabetes 34, 179–184 (1985).PubMedGoogle Scholar
  24. 24.
    D. N. Marreiro, M. Fisberg, and S. M. F. Cozzolino, Zinc nutritional status in obese children and adolescents. Biol. Trace Element Res. 85, 1–16 (2002).CrossRefGoogle Scholar
  25. 25.
    Food and Nutrition Board, Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chormium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium and Zinc, National Academy of Sciences, Washington, DC, (2001).Google Scholar
  26. 26.
    G. J. Brewer, V. Yuzbasiyan-gurkan, V. Johnson, R. D. Dick, and Y. Wang, Treatment of Wilson's disease with zinc: XI. Interation with other anticopper agents, J. Am. Coll. Nutr. 12, 26–30 (1993).PubMedGoogle Scholar
  27. 27.
    M. L. Kennedy and M. L. Failla, Zinc metabilsm in genetically obese (ob/ob) mice, J. Nutr. 117, 886–893 (1987).PubMedGoogle Scholar
  28. 28.
    D. N. Marreiro, M. Fisberg, and S. M. F. Cozzolino, Zinc nutritional status and its relationships with hyperinsulinemia in obese children and adolescents, Biol. Trace Element Res. 100, 137–150 (2004).CrossRefGoogle Scholar
  29. 29.
    M. D. Chen, Y. M. Song, and P. Y. Lin, Zinc effects on hyperglycemia and hypoleptinemia in streptozotocin-induced diabetic mice. Horn. Metab. Res. 32, 107–109 (2000).CrossRefGoogle Scholar
  30. 30.
    P. Sarrat, R. C. Frederich, E. M. Turner, et al., Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia, J. Exp. Med. 185, 171–175 (1997).CrossRefGoogle Scholar
  31. 31.
    T. G. Kirchgessner, K. T. Uysal, S. M. Wiesbrock, M. W. Marino, and G. S. Hotamisligil Tumor necrosis factor a contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J. Clin. Invest. 100, 2777–2782 (1997).PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Dilina do Nascimento Marreiro
    • 1
  • Bruno Geloneze
    • 3
  • Marcos A. Tambascia
    • 3
  • Antonio C. Lerário
    • 2
  • Alfredo Halpern
    • 2
  • Silvia Maria Franciscato Cozzolino
    • 1
  1. 1.Departments of Food Science and Experimental Nutrition, School of PharmacyUniversity of São PauloSão PauloBrazil
  2. 2.Department of EndocrinologyUniversity of São PauloSão PauloBrazil
  3. 3.Department of EndocrinologyUniversity of CampinasSão PauloBrazil

Personalised recommendations