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

Area of Science:

• Endocrinology
• Metabolism
• Bone Biology

Background:

• Fibroblast growth factor 23 (FGF23) regulates phosphate and vitamin D homeostasis.
• Serum FGF23 levels are associated with various disease outcomes.
• Fasting is known to stimulate ketone body production.

Purpose of the Study:

• To investigate if fasting induces FGF23 synthesis via ketone body production.
• To explore the molecular mechanisms linking fasting, ketone bodies, and FGF23.

Main Methods:

• In vitro studies using UMR106 cells and neonatal rat ventricular myocytes (NRVM) treated with β-hydroxybutyrate.
• In vivo studies involving overnight fasting, ad libitum feeding, or β-hydroxybutyrate administration in mice.
• Analysis of FGF23, ketone bodies, vitamin D metabolites, and related gene/protein expression using ELISA, Western blotting, qRT-PCR, and other biochemical assays.

Main Results:

• β-Hydroxybutyrate stimulated FGF23 production in UMR106 cells and NRVMs in a nuclear factor kappa-light-chain enhancer of activated B-cells (NFκB)-dependent manner.
• Fasted mice showed elevated serum β-hydroxybutyrate and FGF23 levels, increased cardiac, pancreatic, and thymic Fgf23 expression, and enhanced renal Cyp24a1 expression compared to fed mice.
• Fasting led to decreased serum 1,25(OH)₂D₃ and renal Slc34a1 and αKlotho (Kl) expression, without significantly altering bone Fgf23 expression or serum phosphate, calcium, PTH, or renal Cyp27b1 levels.

Conclusions:

• Short-term fasting and β-hydroxybutyrate administration increase FGF23 production.
• These findings suggest that the fasting state can influence FGF23 levels, which has potential clinical implications for disease monitoring.
• Fasting-induced FGF23 changes may affect phosphate and vitamin D metabolism.