TY - JOUR
T1 - Fructose increases the activity of sodium hydrogen exchanger in renal proximal tubules that is dependent on ketohexokinase
AU - Hayasaki, Takahiro
AU - Ishimoto, Takuji
AU - Doke, Tomohito
AU - Hirayama, Akiyoshi
AU - Soga, Tomoyoshi
AU - Furuhashi, Kazuhiro
AU - Kato, Noritoshi
AU - Kosugi, Tomoki
AU - Tsuboi, Naotake
AU - Lanaspa, Miguel A.
AU - Johnson, Richard J.
AU - Maruyama, Shoichi
AU - Kadomatsu, Kenji
N1 - Funding Information:
Funding: This work was supported by JSPS KAKENHI grants (15K09255 and JP15K21364), Aichi Kidney Foundation (26 ZAIAIJINN 41-5), JSPS KAKENHI (JP15K21364), and NIH grants (NIDDK 1RO1DK109408-01A1 and NIDDK R01 DK108859-01. Funding: This work was supported by JSPS KAKENHI grants ( 15K09255 and JP15K21364), Aichi Kidney Foundation ( 26 ZAIAIJINN 41-5), JSPS KAKENHI ( JP15K21364), and NIH grants (NIDDK 1RO1DK109408-01A1 and NIDDK R01 DK108859-01. We thank Noriyuki Suzuki, Naoko Asano, Yuriko Sawa, and Eri Yorifuji, for their excellent assistance. We thank Satsuki Ikeda and Yu-yu Kato for performing the metabolomic analysis. Funding: This work was supported by JSPS KAKENHI grants ( 15K09255 and JP15K21364), Aichi Kidney Foundation ( 26 ZAIAIJINN 41-5), JSPS KAKENHI ( JP15K21364), and NIH grants (NIDDK 1RO1DK109408-01A1 and NIDDK R01 DK108859-01.
PY - 2019/9
Y1 - 2019/9
N2 - High fructose intake has been known to induce metabolic syndrome in laboratory animals and humans. Although fructose intake enhances sodium reabsorption and elevates blood pressure, role of fructose metabolism in this process has not been studied. Here we show that by ketohexokinase — the primary enzyme of fructose — is involved in regulation of renal sodium reabsorption and blood pressure via activation of the sodium hydrogen exchanger in renal proximal tubular cells. First, wild-type and ketohexokinase knockout mice (Male, C57BL/6) were fed fructose water or tap water with or without a high salt diet. Only wild type mice fed the combination of fructose water and high salt diet displayed increased systolic blood pressure and decreased urinary sodium excretion. In contrast, ketohexokinase knockout mice were protected. Second, urinary sodium excretion after intraperitoneal saline administration was reduced with the decreased phosphorylation of sodium hydrogen exchanger 3 in fructose-fed WT; these changes were not observed in the ketohexokinase knockout mice, however. Third, knockdown of ketohexokinase attenuated fructose-mediated increases of NHE activity with decreased cAMP levels in porcine renal proximal tubular cells (LLC-PK1). In conclusion, fructose metabolism by ketohexokinase increases sodium hydrogen exchanger activity in renal proximal tubular cells via decreased intracellular cAMP level, resulting in increased renal sodium reabsorption and blood pressure in mice.
AB - High fructose intake has been known to induce metabolic syndrome in laboratory animals and humans. Although fructose intake enhances sodium reabsorption and elevates blood pressure, role of fructose metabolism in this process has not been studied. Here we show that by ketohexokinase — the primary enzyme of fructose — is involved in regulation of renal sodium reabsorption and blood pressure via activation of the sodium hydrogen exchanger in renal proximal tubular cells. First, wild-type and ketohexokinase knockout mice (Male, C57BL/6) were fed fructose water or tap water with or without a high salt diet. Only wild type mice fed the combination of fructose water and high salt diet displayed increased systolic blood pressure and decreased urinary sodium excretion. In contrast, ketohexokinase knockout mice were protected. Second, urinary sodium excretion after intraperitoneal saline administration was reduced with the decreased phosphorylation of sodium hydrogen exchanger 3 in fructose-fed WT; these changes were not observed in the ketohexokinase knockout mice, however. Third, knockdown of ketohexokinase attenuated fructose-mediated increases of NHE activity with decreased cAMP levels in porcine renal proximal tubular cells (LLC-PK1). In conclusion, fructose metabolism by ketohexokinase increases sodium hydrogen exchanger activity in renal proximal tubular cells via decreased intracellular cAMP level, resulting in increased renal sodium reabsorption and blood pressure in mice.
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U2 - 10.1016/j.jnutbio.2019.05.017
DO - 10.1016/j.jnutbio.2019.05.017
M3 - Article
C2 - 31276916
AN - SCOPUS:85068240184
VL - 71
SP - 54
EP - 62
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
SN - 0955-2863
ER -