Short‐term fasting of mice elevates circulating fibroblast growth factor 23 (FGF23)

Abstract

AimsPhosphate and vitamin D homeostasis are controlled by fibroblast growth factor 23 (FGF23) from bone suppressing renal phosphate transport and enhancing 24‐hydroxylase (Cyp24a1), thereby inactivating 1,25(OH)2D3. Serum FGF23 is correlated with outcomes in several diseases. Fasting stimulates the production of ketone bodies. We hypothesized that fasting can induce FGF23 synthesis through the production of ketone bodies.MethodsUMR106 cells and isolated neonatal rat ventricular myocytes (NRVM) were treated with ketone body β‐hydroxybutyrate. Mice were fasted overnight, fed ad libitum, or treated with β‐hydroxybutyrate. Proteins and further blood parameters were determined by enzyme‐linked immunoassay (ELISA), western blotting, immunohistochemistry, fluorometric or colorimetric methods, and gene expression by quantitative real‐time polymerase chain reaction (qRT‐PCR).Resultsβ‐Hydroxybutyrate stimulated FGF23 production in UMR106 cells in a nuclear factor kappa‐light‐chain enhancer of activated B‐cells (NFκB)‐dependent manner, and in NRVMs. Compared to fed animals, fasted mice exhibited higher β‐hydroxybutyrate and FGF23 serum levels (based on assays either detecting C‐terminal or intact, biologically active FGF23 only), cardiac, pancreatic, and thymic Fgf23 and renal Cyp24a1 expression, and lower 1,25(OH)2D3 serum concentration as well as renal Slc34a1 and αKlotho (Kl) expression. In contrast, Fgf23 expression in bone and serum phosphate, calcium, plasma parathyroid hormone (PTH) concentration, and renal Cyp27b1 expression were not significantly affected by fasting.ConclusionShort‐term fasting increased FGF23 production, as did administration of β‐hydroxybutyrate, effects possibly of clinical relevance in view of the increasing use of FGF23 as a surrogate parameter in clinical monitoring of diseases. The fasting state of patients might therefore affect FGF23 tests.

Recent advances in kidney research

“…The kidney has several endocrine roles, secreting both hormones and humoral factors of, for example, the renin‐ angiotensin system (RAS), erythropoietin (EPO), and 1,25 dihydroxy vitamin D3. It is critically involved in vitamin D and phosphate homeostasis, which are both modulated by the by fibroblast growth factor 23 (FGF23) 1 . In this study by Feger et al.…”

“…It is critically involved in vitamin D and phosphate homeostasis, which are both modulated by the by fibroblast growth factor 23 (FGF23). 1 In this study by Feger et al the effect of short term fasting on FGF23 were analyzed. The experiments were performed in cell cultures of rat myocytes as well as in mice that were fasted overnight.…”