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ID 119347
Title Alternative
5/6腎臓摘出ラットにおいて増加する腸管腔内無機リン酸は亜鉛吸収を抑制する
INORGANIC PHOSPHATE SUPPRESSES INTESTINAL Zn ABSORPTION
Author
Okumura, Yosuke Tokushima University
Abe, Kotaro Tokushima University
Sakai, Shoko Tokushima University
Mori, Yuki Tokushima University
Adachi, Yuichiro Tokushima University
Takikawa, Masaki Tokushima University
Kitamura, Ayano Tokushima University
Ohnishi, Kohta Tokushima University
Kambe, Taiho Kyoto University
Keywords
chronic kidney disease
zinc deficiency
hyperphosphatemia
dietary phosphate
zinc transporter
Content Type
Thesis or Dissertation
Description
Zinc (Zn) is an essential trace element in various biological processes. Chronic kidney disease (CKD) often leads to hypozincemia, resulting in further progression of CKD. In CKD, intestinal Zn absorption, the main regulator of systemic Zn metabolism, is often impaired; however, the mechanism underlying Zn malabsorption remains unclear. Here, we evaluated intestinal Zn absorption capacity in a rat model of CKD induced by 5/6 nephrectomy (5/6 Nx). Rats were given Zn and the incremental area under the plasma Zn concentration-time curve (iAUC) was measured as well as the expression of ZIP4, an intestinal Zn transporter. We found that 5/6 Nx rats showed lower iAUC than sham-operated rats, but expression of ZIP4 protein was upregulated. We therefore focused on other Zn absorption regulators to explore the mechanism by which Zn absorption was substantially decreased. Because some phosphate compounds inhibit Zn absorption by coprecipitation and hyperphosphatemia is a common symptom in advanced CKD, we measured inorganic phosphate (Pi) levels. Pi was elevated in not only serum but also the intestinal lumen of 5/6 Nx rats. Furthermore, intestinal intraluminal Pi administration decreased the iAUC in a dose-dependent manner in normal rats. In vitro, increased Pi concentration decreased Zn solubility under physiological conditions. Furthermore, dietary Pi restriction ameliorated hypozincemia in 5/6 Nx rats. We conclude that hyperphosphatemia or excess Pi intake is a factor in Zn malabsorption and hypozincemia in CKD. Appropriate management of hyperphosphatemia will be useful for prevention and treatment of hypozincemia in patients with CKD.
NEW & NOTEWORTHY We demonstrated that elevated intestinal luminal Pi concentration can suppress intestinal Zn absorption activity without decreasing the expression of the associated Zn transporter. Increased intestinal luminal Pi led to the formation of an insoluble complex with Zn while dietary Pi restriction or administration of a Pi binder ameliorated hypozincemia in chronic kidney disease model rats. Therefore, modulation of dietary Pi by Pi restriction or a Pi binder might be useful for the treatment of hypozincemia and hyperphosphatemia.
Journal Title
American Journal of Physiology-Renal Physiology
ISSN
1931857X
15221466
NCID
AA11118857
AA12070596
Publisher
American Physiological Society
Volume
326
Issue
3
Start Page
F411
End Page
F419
Published Date
2024-02-21
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Yosuke Okumuraの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3807号
Diploma Number
甲栄第306号
Granted Date
2024-03-22
Degree Name
Doctor of Nutritional Science
Grantor
Tokushima University
departments
Medical Sciences