title: Effects of dietary iron intake and chronic kidney disease on fibroblast growth factor 23 metabolism in wild-type and hepcidin knockout mice.
abstract: In the setting of normal kidney function, iron deficiency is associated with increased FGF23 production and cleavage, altering circulating FGF23 levels. Our objective was to determine how chronic kidney disease (CKD) and dietary iron intake affect FGF23 production and metabolism in wild-type (WT) and hepcidin knockout (HKO) mice. For 8 wk, the mice were fed diets that contained adenine (to induce CKD) or no adenine (control group), with either low-iron (4 ppm) or standard-iron (335 ppm) concentrations. The low-iron diet induced iron deficiency anemia in both the WT and HKO mice. Among the WT mice, in both the control and CKD groups, a low-iron compared with a standard-iron diet increased bone Fgf23 mRNA expression, C-terminal FGF23 (cFGF23) levels, and FGF23 cleavage as manifested by a lower percentage intact FGF23 (iFGF23). Independent of iron status, CKD was associated with inhibition of FGF23 cleavage. Similar results were observed in the HKO control and CKD groups. Dietary iron content was more influential on FGF23 parameters than the presence or absence of hepcidin. In the CKD mice (WT and HKO, total n = 42), independent of the effects of serum phosphate, iron deficiency was associated with increased FGF23 production but also greater cleavage, whereas worse kidney function was associated with increased FGF23 production but decreased cleavage. Therefore, in both the WT and HKO mouse models, dietary iron content and CKD affected FGF23 production and metabolism.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California; mhanudel@mednet.ucla.edu.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hanudel
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; and.
authors.forename: Kristine
authors.initials: K
authors.lastname: Chua
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Maxime
authors.initials: M
authors.lastname: Rappaport
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; and.
authors.forename: Victoria
authors.initials: V
authors.lastname: Gabayan
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; and.
authors.forename: Erika
authors.initials: E
authors.lastname: Valore
authors.affiliation: Department of Medicine, McGill University Health Centre and McGill University, Montreal, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Goltzman
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; and.
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; and.
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Isidro B
authors.initials: IB
authors.lastname: Salusky
mesh_terms: D000225:Adenine; D000818:Animals; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism; D019266:Iron, Dietary / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000378:metabolism*
chemical_list: C000717428:Fgf23 protein, mouse; D064451:Hepcidins; D019266:Iron, Dietary; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000225:Adenine
keywords: chronic kidney disease; fibroblast growth factor 23; hepcidin; iron deficiency anemia