Pflügers Archiv - European Journal of Physiology

, Volume 466, Issue 3, pp 467–475

Regulation of mineral metabolism by lithium

  • Hajar Fakhri
  • Ganesh Pathare
  • Abul Fajol
  • Bingbing Zhang
  • Thomas Bock
  • Reinhard Kandolf
  • Erwin Schleicher
  • Jürg Biber
  • Michael Föller
  • Undine E. Lang
  • Florian Lang
Integrative physiology

Abstract

Lithium, an inhibitor of glycogen synthase kinase 3 (GSK3), is widely used for the treatment of mood disorders. Side effects of lithium include nephrogenic diabetes insipidus, leading to renal water loss. Dehydration has in turn been shown to downregulate Klotho, which is required as co-receptor for the downregulation of 1,25(OH)2D3 formation by fibroblast growth factor 23 (FGF23). FGF23 decreases and 1,25(OH)2D3 stimulates renal tubular phosphate reabsorption. The present study explored whether lithium influences renal Klotho expression, FGF23 serum levels, 1,25(OH)2D3 formation, and renal phosphate excretion. To this end, mice were analyzed after a 14-day period of sham treatment or of treatment with lithium (200 mg/kg/day subcutaneously). Serum antidiuretic hormone (ADH), FGF23, and 1,25(OH)2D3 concentrations were determined by ELISA or EIA, renal Klotho protein abundance and GSK3 phosphorylation were analyzed by Western blotting, and serum phosphate and calcium concentration by photometry. Lithium treatment significantly increased renal GSK3 phosphorylation, enhanced serum ADH and FGF23 concentrations, downregulated renal Klotho expression, stimulated renal calcium and phosphate excretion, and decreased serum 1,25(OH)2D3 and phosphate concentrations. In conclusion, lithium treatment upregulates FGF23 formation, an effect paralleled by substantial decrease of serum 1,25(OH)2D3, and phosphate concentrations and thus possibly affecting tissue calcification.

Keywords

Lithium FGF23 Klotho 1,25(OH)2D3 Phosphate Calcium 

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Hajar Fakhri
    • 1
  • Ganesh Pathare
    • 1
  • Abul Fajol
    • 1
  • Bingbing Zhang
    • 1
    • 2
  • Thomas Bock
    • 2
  • Reinhard Kandolf
    • 2
  • Erwin Schleicher
    • 3
  • Jürg Biber
    • 4
  • Michael Föller
    • 1
  • Undine E. Lang
    • 5
  • Florian Lang
    • 1
    • 6
  1. 1.Department of PhysiologyUniversity of TübingenTübingenGermany
  2. 2.Department of Molecular PathologyUniversity of TübingenTübingenGermany
  3. 3.Department of Internal Medicine IVUniversity of TübingenTübingenGermany
  4. 4.Department of PhysiologyUniversity of ZürichZürichSwitzerland
  5. 5.Department of PsychiatryUniversity of BaselBaselSwitzerland
  6. 6.Physiologisches Institut der Universität TübingenTübingenGermany

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