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Lithocholic acid increases intestinal phosphate and calcium absorption in a vitamin D receptor dependent but transcellular pathway independent manner.
Hashimoto, Nobuhiro; Matsui, Isao; Ishizuka, Satoshi; Inoue, Kazunori; Matsumoto, Ayumi; Shimada, Karin; Hori, Shota; Lee, Dong Geun; Yasuda, Seiichi; Katsuma, Yusuke; Kajimoto, Sachio; Doi, Yohei; Yamaguchi, Satoshi; Kubota, Keiichi; Oka, Tatsufumi; Sakaguchi, Yusuke; Takabatake, Yoshitsugu; Hamano, Takayuki; Isaka, Yoshitaka.
Afiliación
  • Hashimoto N; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Matsui I; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: matsui@kid.med.osaka-u.ac.jp.
  • Ishizuka S; Division of Fundamental Agriscience Research, Research Faculty of Agriculture, Hokkaido University, Kita-ku, Sapporo, Japan.
  • Inoue K; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Matsumoto A; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Shimada K; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Hori S; Division of Fundamental Agriscience Research, Research Faculty of Agriculture, Hokkaido University, Kita-ku, Sapporo, Japan.
  • Lee DG; Division of Fundamental Agriscience Research, Research Faculty of Agriculture, Hokkaido University, Kita-ku, Sapporo, Japan.
  • Yasuda S; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Katsuma Y; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Kajimoto S; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Doi Y; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Yamaguchi S; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Kubota K; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Oka T; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Sakaguchi Y; Department of Inter-Organ Communication Research in Kidney Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Takabatake Y; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Hamano T; Department of Inter-Organ Communication Research in Kidney Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
  • Isaka Y; Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kidney Int ; 97(6): 1164-1180, 2020 06.
Article en En | MEDLINE | ID: mdl-32354638
Phosphate/calcium homeostasis is crucial for health maintenance. Lithocholic acid, a bile acid produced by intestinal bacteria, is an agonist of vitamin D receptor. However, its effects on phosphate/calcium homeostasis remain unclear. Here, we demonstrated that lithocholic acid increases intestinal phosphate/calcium absorption in an enterocyte vitamin D receptor-dependent manner. Lithocholic acid was found to increase serum phosphate/calcium levels and thus to exacerbate vascular calcification in animals with chronic kidney disease. Lithocholic acid did not affect levels of intestinal sodium-dependent phosphate transport protein 2b, Pi transporter-1, -2, or transient receptor potential vanilloid subfamily member 6. Everted gut sac analyses demonstrated that lithocholic acid increased phosphate/calcium absorption in a transcellular pathway-independent manner. Lithocholic acid suppressed intestinal mucosal claudin 3 and occludin in wild-type mice, but not in vitamin D receptor knockout mice. Everted gut sacs of claudin 3 knockout mice showed an increased permeability for phosphate, but not calcium. In patients with chronic kidney disease, serum 1,25(OH)2 vitamin D levels are decreased, probably as an intrinsic adjustment to reduce phosphate/calcium burden. In contrast, serum and fecal lithocholic acid levels and fecal levels of bile acid 7α-dehydratase, a rate-limiting enzyme involved in lithocholic acid production, were not downregulated. The effects of lithocholic acid were eliminated by bile acid adsorptive resin in mice. Thus, lithocholic acid and claudin 3 may represent novel therapeutic targets for reducing phosphate burden.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcio / Receptores de Calcitriol Límite: Animals / Humans Idioma: En Revista: Kidney Int Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcio / Receptores de Calcitriol Límite: Animals / Humans Idioma: En Revista: Kidney Int Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos