title: Regulation of mineral metabolism by lithium.
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.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Hajar
authors.initials: H
authors.lastname: Fakhri
authors.forename: Ganesh
authors.initials: G
authors.lastname: Pathare
authors.forename: Abul
authors.initials: A
authors.lastname: Fajol
authors.forename: Bingbing
authors.initials: B
authors.lastname: Zhang
authors.forename: Thomas
authors.initials: T
authors.lastname: Bock
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.forename: Erwin
authors.initials: E
authors.lastname: Schleicher
authors.forename: Jürg
authors.initials: J
authors.lastname: Biber
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Undine E
authors.initials: UE
authors.lastname: Lang
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000090265:Klotho Proteins; D008094:Lithium / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010710:Phosphates / Q000097:blood / Q000378:metabolism* / Q000652:urine
chemical_list: C000717428:Fgf23 protein, mouse; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D008094:Lithium; D005966:Glucuronidase; D000090265:Klotho Proteins; D002117:Calcitriol; D002118:Calcium