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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
著者
奥村, 陽介 徳島大学大学院医科栄養学研究科(医科栄養学専攻)
Abe, Kotaro Tokushima University
Sakai, Shoko Tokushima University
Mori, Yuki Tokushima University
Adachi, Yuichiro Tokushima University
Takikawa, Masaki Tokushima University
Kitamura, Ayano Tokushima University
大西, 康太 Tokushima University
Kambe, Taiho Kyoto University
キーワード
chronic kidney disease
zinc deficiency
hyperphosphatemia
dietary phosphate
zinc transporter
資料タイプ
学位論文
抄録
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.
掲載誌名
American Journal of Physiology-Renal Physiology
ISSN
1931857X
15221466
cat書誌ID
AA11118857
AA12070596
出版者
American Physiological Society
326
3
開始ページ
F411
終了ページ
F419
発行日
2024-02-21
備考
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
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3807号
学位記番号
甲栄第306号
学位授与年月日
2024-03-22
学位名
博士(栄養学)
学位授与機関
徳島大学
部局
医学系