Regulation of α-Klotho Expression by Dietary Phosphate During Growth Periods
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Inorganic phosphate (Pi) is an essential nutrient for maintaining various biological functions, particularly during growth periods. Excess intake of dietary Pi increases the secretion of fibroblast growth factor 23 (FGF23) and parathyroid hormone to maintain plasma Pi levels. FGF23 is a potent phosphaturic factor that binds to the α-klotho/FGFR complex in the kidney to promote excretion of Pi into the urine. In addition, excess intake of dietary Pi decreases renal α-klotho expression. Down-regulation or lack of α-klotho induces a premature aging-like phenotype, resulting from hyperphosphatemia, and leading to conditions such as ectopic calcification and osteoporosis. However, it remains unclear what effects dietary Pi has on α-klotho expression at different life stages, especially during growth periods. To investigate this, we used C57BL/6J mice in two life stages during growing period. Weaned (3 weeks old) and periadolescent (7 weeks old) were randomly divided into seven experimental groups and fed with 0.02, 0.3, 0.6, 0.9, 1.2, 1.5, or 1.8% Pi diets for 7 days. As a result, elevated plasma Pi and FGF23 levels and decreased renal α-klotho expression were observed in weaned mice fed with a high Pi diet. In addition, a high Pi diet clearly induced renal calcification in the weaned mice. However, in the periadolescent group, renal calcification was not observed, even in the 1.8% Pi diet group. The present study indicates that a high Pi diet in weaned mice has much greater adverse effects on renal α-klotho expression and pathogenesis of renal calcification compared with periadolescent mice.
KeywordsDietary phosphate Growth periods α-Klotho FGF23 Vitamin D metabolism Kidney
We thank Shoko Ikeda, Mari Nakao, Nozomi Yokoyama, Rina Onishi, Kazuki Fujimoto, Natsuki Oka (Department of Clinical Nutrition and Food Management, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan) for technical assistance.
Funding was provided by Japan Society for the Promotion of Science (Grant No. 16H03046).
Compliance with Ethical Standards
Conflict of interest
Shiori Fukuda-Tatano, Hironori Yamamoto, Otoki Nakahashi, Ryouhei Yoshikawa, Mayu Hayashi, Maki Kishimoto, Yukiko Imi, Hisami Yamanaka-Okumura, Kohta Ohnishi, Masashi Masuda, and Yutaka Taketani declare no conflicts of interest.
Human and Animal Rights and Informed Consent
The present study was approved by the Animal Experimentation Committee of Tokushima University and was conducted in accordance with the guidelines for the management and handling of experimental animals.
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