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Abstract: FR-PO258

Lithocholic Acid Increases Plasma Levels of FGF23

Session Information

Category: Mineral Disease

  • 1202 Mineral Disease: Vitamin D, PTH, FGF-23

Authors

  • Hashimoto, Nobuhiro, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Matsui, Isao, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Mori, Daisuke, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Matsumoto, Ayumi, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Shimada, Karin, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Yamaguchi, Satoshi, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Kubota, Keiichi, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Oka, Tatsufumi, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Yonemoto, Sayoko, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Sakaguchi, Yusuke, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Hamano, Takayuki, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Isaka, Yoshitaka, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
Background

The phosphate sensing mechanisms remain unresolved. Oral phosphate load can increase fibroblast growth factor 23 (FGF23) without affecting serum levels of phosphate. Vitamin D receptor (VDR) plays important roles in the regulation of FGF23. In addition to active vitamin D, lithocholic acid (LCA), a secondary bile acid, can activate VDR. Therefore, we examined effects of LCA on FGF23.

Methods

Vitamin D receptor knockout (VDR-KO) mice and their wild type (WT) littermates were maintained on rescue diet (20% lactose, 2% Ca, 1.25% P). Mice fed with diet containing 0.2% cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), or lithocholic acid (LCA) were analyzed. Effects of bile acids in vitro were analyzed by using UMR106 cells. Gut flora of phosphate loaded mice were analyzed by PCR.

Results

Orally administered LCA elevated plasma intact FGF23 (WT-control 97 ± 35 vs. WT-LCA 204 ± 62 pg/mL, P <0.001). The other bile acids did not affect plasma iFGF23. LCA increased urinary phosphate, whereas serum phosphate was not changed. In VDR-KO mice, whose serum calcium levels were corrected to normal range by the rescue diet, the effects of LCA were completely abrogated. Real time PCR analyses of the WT mice demonstrated that LCA upregulated mRNA of FGF23 in the bone. We also found that LCA upregulates mRNA levels of FGF23 in cultured UMR 106 cells. Because serum 1,25-dihydroxyvitamin D was suppressed by LCA in the WT mice, it was indicated that LCA per se elevated FGF23 in a VDR-dependent manner. We examined serum creatinine and urinary N-acetyl-β-D-glucosaminidase levels because kidney function is a critical determinant of plasma FGF23. LCA did not worsen kidney function. Dietary phosphate load increased fecal Firmicutes XIVa, an intestinal bacteria that produces secondary bile acid.

Conclusion

Oral administration of LCA elevates FGF23 in a VDR-dependent manner. The change in gut microbiota may contribute to the phosphate sensing mechanism.