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Linking Zinc and Leptin in Chronic Kidney Disease: Future Directions

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Abstract

Anorexia is a common complication in patients with chronic kidney disease (CKD) and is associated with the development of malnutrition and an increased risk of mortality. Several compounds are linked to anorexia in these patients; however, the mechanisms are unknown. Zinc (Zn) deficiency is associated with decreased food intake and has been observed in CKD patients. In addition, leptin is an anorexigenic peptide, and patients with CKD present generally high levels of this hormone. Studies have suggested an association between Zn and leptin status in human and rats; however, the results are inconsistent. Some claimed that Zn supplementation does not change leptin release or that there is no significant relationship between Zn and leptin. Others have reported that Zn might be a mediator of leptin production. CKD patients have hyperleptinemia and hypozincemia, but the relationship between Zn deficiency and leptin levels in CKD patients has been poorly understood until now. The aim of this review is to integrate knowledge on leptin and Zn actions to provide a cohesive clinical perspective regarding their interactions in CKD patients.

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References

  1. Bossola M, Tazza L, Giungi S et al (2006) Anorexia in hemodialysis patients: an update. Kidney Int 70:417–422

    PubMed  CAS  Google Scholar 

  2. Carrero JJ, Aguilera A, Stenvinkel P et al (2008) Appetite disorders uremia. J Ren Nutr 18:107–113

    Article  PubMed  Google Scholar 

  3. Kaji M (2001) Zinc in endocrinology. Int Pediatr 16:1–7

    Google Scholar 

  4. Sun JY, Jing MY, Weng XY et al (2005) Effects of dietary zinc levels on the activities of enzymes, weights of organs and the concentrations of zinc and copper in growing rats. Biol Trace Elem Res 107:153–165

    Article  PubMed  CAS  Google Scholar 

  5. Sun JY, Wang JF, Zi NT et al (2007) Gene expression profiles analysis of the growing rat liver in response to different zinc status by cDNA microarray analysis. Biol Trace Elem Res 115:157–185

    Article  Google Scholar 

  6. Mantzoros CS, Prasad AS, Beck FWJ et al (1998) Zinc may regulate serum leptin concentrations in humans. J Am Coll Nutr 17:270–275

    PubMed  CAS  Google Scholar 

  7. Otero M, Lago R, Lago F et al (2005) Leptin, from fat to inflammation: old questions and new insights. FEBS Lett 579:295–301

    Article  PubMed  CAS  Google Scholar 

  8. Mak RH, CheungW CRD et al (2006) Leptn and inflammation-associated cachexia in chronic kidney disease. Kidney Int 69:794–797

    Article  PubMed  CAS  Google Scholar 

  9. Mangian H, Lee R, Paul G et al (1998) Zinc deficiency suppresses plasma leptin concentrations in rats. Nutr Biochem 9:47–51

    Article  CAS  Google Scholar 

  10. Ott E, Shay NF (2001) Zinc deficiency reduces leptin gene expression and leptin secretion in rat adipocytes. Exp Biol Med 226:841–846

    CAS  Google Scholar 

  11. Ninh NX, Thissen JP, Collette L et al (1996) Zinc supplementation increases growth and circulating insulin-like growth factor I (IGF-I) in growth retarded Vietnamese children. Am J Clin Nutr 63:514–519

    PubMed  CAS  Google Scholar 

  12. Shay NF, Mangian HF (2000) Neurobiology of zinc-influenced eating behavior. J Nutr 130:1493–1499

    Google Scholar 

  13. Jing MY, Sun JY, Weng XY (2007) Insights on zinc regulation of food intake and macronutrient selection. Biol Trace Elem Res 115:187–194

    Article  PubMed  CAS  Google Scholar 

  14. Huntington CE, Shay NF, Grouzmann E et al (2002) Zinc status affects neurotransmitter activity in the paraventricular nucleus of rats. J Nutr 132:270–275

    PubMed  CAS  Google Scholar 

  15. Levenson CW (2003) Zinc regulation of food intake: new insights on the role of neuropeptide Y. Nutr Rev 61:247–258

    Article  PubMed  Google Scholar 

  16. Woods SC (2005) Signals that influence food intake and body weight. Physiol Behav 86:709–716

    Article  PubMed  CAS  Google Scholar 

  17. Kennedy KJ, Rains TM, Shay NF (1998) Zinc deficiency changes preferred macronutrient intake in subpopulations of Sprague–Dawley outbred rats and reduces hepatic pyruvate kinase gene expression. J Nutr 128:43–49

    PubMed  CAS  Google Scholar 

  18. Blundell E (1984) Serotonin and appetite. Neuropharmacology 23:1537–1551

    Article  PubMed  CAS  Google Scholar 

  19. Tallman DL, Taylor CG (2003) Effects of dietary fat and zinc on adiposity, serum leptin and adipose fatty acid composition in C57BL/6J mice. J Nutr Biochem 14:17–23

    Article  PubMed  CAS  Google Scholar 

  20. Halaas JL, Gajiwala KS, Maffei M et al (1995) Weight-reducing effects of the plasma-protein encoded bythe obese. Gene Sci 269:543–546

    CAS  Google Scholar 

  21. Pelleymounter MA, Cullen MJ, Baker MB et al (1995) Effects of the obese gene product on body-weight regulation in Ob/Ob Mice. Science 269:540–543

    Article  PubMed  CAS  Google Scholar 

  22. Frühbeck G (2006) Intracellular signaling pathways activated by leptin. Biochem J 393:7–20

    Article  PubMed  Google Scholar 

  23. Arora S, Anubhuti (2006) Role of neuropeptides in appetite regulation and obesity—a review. Neuropeptides 40:375–401

    Article  PubMed  CAS  Google Scholar 

  24. Bribiescas RG (2003) Effects of oral zinc supplementation on serum leptin levels in Ache males of eastern Paraguay. Am J Hum Biol 15:681–687

    Article  PubMed  Google Scholar 

  25. Olusi S, Al-Awadhi A, Abiaka C et al (2003) Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population. Biol Trace Elem Res 91:137–144

    Article  PubMed  CAS  Google Scholar 

  26. Chen MD, Song YM, Lin PY (2000) Zinc may be a mediator of leptin production in humans. Life Sci 21:2143–2149

    Article  Google Scholar 

  27. Kwun IS, Cho YE, Lomeda RA et al (2007) Marginal zinc deficiency in rats decreases leptin expression independently of food intake and corticotrophin-releasing hormone in relation to food intake. Br J Nutr 98:485–489

    Article  PubMed  CAS  Google Scholar 

  28. Baltaci AK, Mogulkoc R, Halifeoglu I (2005) Effects of zinc deficiency and supplementation on plasma leptin levels in rats. Biol Trace Elem Res 104:41–46

    Article  PubMed  CAS  Google Scholar 

  29. Chen MD, Lin PY (2000) Zinc-induced hyperleptinemia relates to the amelioration of sucrose-induced obesity with zinc repletion. Obes Res 8:525–529

    Article  PubMed  CAS  Google Scholar 

  30. Lee SL, Kwak EH, Kim YH et al (2003) Leptin gene expression and serum leptin levels in zinc deficiency: implications for appetite regulation in rats. J Med Food 6:281–289

    Article  PubMed  CAS  Google Scholar 

  31. Konukoglu D, Thurhan MS, Ercan M et al (2004) Relationship between plasma leptin and zinc levels and the effect of insulin and oxidative stress on leptin levels in obese diabetic patients. J Nutr Biochem 15:757–760

    Article  PubMed  CAS  Google Scholar 

  32. Faure P, Roussel A, Coundray C et al (1992) Zinc and insulin sensitivity. Biol Trace Elem Res 32:305–310

    Article  PubMed  CAS  Google Scholar 

  33. García OP, Long KZ, Rosado JL (2009) Impact of micronutrient deficiencies on obesity. Nutr Rev 67:559–72

    Article  PubMed  Google Scholar 

  34. Mafra D, Cuppari L, Cozzolino SM (2002) Iron and zinc status of patients with chronic renal failure who are not on dialysis. J Ren Nutr 12:38–41

    Article  PubMed  Google Scholar 

  35. Sharupskiene I, Kuzminskis V, Abdrachamanovas O et al (2004) Zinc and aluminum concentrations in blood of hemodialysis patients and its impact on the frequency of infections. Medicina (Kaunas) 41:65–68

    Google Scholar 

  36. Cabral PC, Diniz AS, de Arruda IK (2005) Vitamin A and zinc status in patients on maintenance haemodialysis. Nephrology (Carlton) 10:459–463

    Article  CAS  Google Scholar 

  37. Bozalioglu S, Ozkan Y, Turan M et al (2005) Prevalence of zinc deficiency and immune response in short-term hemodialysis. J Trace Elem Med Biol 18:243–249

    Article  PubMed  CAS  Google Scholar 

  38. Esfahani ST, Hamidian MR, Madani A et al (2006) Serum zinc and copper levels in children with chronic renal failure. Pediatr Nephrol 21:1153–1156

    Article  PubMed  Google Scholar 

  39. Zwolinska D, Grzeszczak W, Szczepanska M et al (2006) Lipid peroxidation and antioxidant enzymes in children on maintenance dialysis. Pediatr Nephrol 21:705–710

    Article  PubMed  Google Scholar 

  40. Vanholder R, Van Loo A, Dhondt AM et al (1996) Influence of uraemia and haemodialysis on host defence and infection. Nephrol Dial Transplant 11:593–598

    PubMed  CAS  Google Scholar 

  41. Mak RH, CheungW CRD et al (2006) Leptin and inflammation-associated cachexia in chronic kidney disease. Kidney Int 69:794–797

    Article  PubMed  CAS  Google Scholar 

  42. Aminzadeh MA, Pahl VM, Borton CH et al (2009) Human uraemic plasma stimulates release of leptin and uptake of tumour necrosis factor-α in visceral adipocytes. Nephrol Dial Transplant 24:3626–3631

    Article  PubMed  CAS  Google Scholar 

  43. Horoz M, Aslan M, Koylu AO et al (2009) The relationship between leptin level and oxidative status parameters in hemodialysis patients. Artif Organs 33:81–85

    Article  PubMed  Google Scholar 

  44. Nordfors L, Lonnqvist F, Heimburger O et al (1998) Low leptin gene expression and hyperleptinemia in chronic renal failure. Kidney Int 54:1267–1275

    Article  PubMed  CAS  Google Scholar 

  45. Stenvinkel P (1998) Leptin—a new hormone of definite interest for the nephrologist. Nephrol DialTransplant 13:1099–1101

    CAS  Google Scholar 

  46. Castaneda-Sceppa C, Sarnak MJ, Wang X et al (2007) Role of adipose tissue in determining muscle mass in patients with chronic kidney disease. J Ren Nutr 17:314–322

    Article  PubMed  Google Scholar 

  47. Stenvinkel P, Lindholm B, Lonnqvist F et al (2000) Increases in serum leptin levels during peritoneal dialysis are associated with inflammation and a decrease in lean body mass. J Am Soc Nephrol 11:1303–1309

    PubMed  CAS  Google Scholar 

  48. Lam MF, Leung JC, Lo WK et al (2007) Hyperleptinaemia and chronic inflammation after peritonitis predicts poor nutritional status and mortality in patients on peritoneal dialysis. Nephrol Dial Transplant 22:1445–1450

    Article  PubMed  CAS  Google Scholar 

  49. Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783

    Article  PubMed  CAS  Google Scholar 

  50. Sahin H, Uyanik F, Inanç N et al (2008) Serum zinc, plasma ghrelin, leptin levels, selected biochemical parameters and nutritional status in malnourished hemodialysis patients. Biol Trace Elem Res 127:191–199

    Article  PubMed  Google Scholar 

  51. Mafra D, Aranha LN, Lobo J, Stockler-Pinto MB, Leal VO, Farage NE, Fouque D (2010) Zinc may regulate serum leptin concentrations in hemodialysis patients. Renal Week 2010 Annals: ASN

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Acknowledgements

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) are gratefully acknowledged.

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Authors and Affiliations

  1. Federal University of Rio de Janeiro (UFRJ), Institute of Biophysic Carlos Chagas Filho, Health Science Centre, Rio de Janeiro, Brazil

    Julie Calixto Lobo

  2. Department of Clinical Nutrition, Federal Fluminense University (UFF), Niterói, Brazil

    Luciana Nicolau Aranha, Cristiane Moraes & Denise Mafra

  3. Faculty of Clinical Nutrition, Federal University of Sergipe (UFS), Aracaju, Brazil

    Luciana Catunda Brito

  4. Rua Alzira Cortes, 05 apto 106, Botafogo, Rio de Janeiro, Brazil

    Denise Mafra

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  1. Julie Calixto Lobo
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  2. Luciana Nicolau Aranha
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  3. Cristiane Moraes
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  4. Luciana Catunda Brito
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  5. Denise Mafra
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Correspondence to Denise Mafra.

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Lobo, J.C., Aranha, L.N., Moraes, C. et al. Linking Zinc and Leptin in Chronic Kidney Disease: Future Directions. Biol Trace Elem Res 146, 1–5 (2012). https://doi.org/10.1007/s12011-011-9211-x

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  • DOI: https://doi.org/10.1007/s12011-011-9211-x

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