Kidney Week

Abstract: FR-PO324

Up-regulation of SGLT-5 as a Cause of Fructose-Induced Volume-Dependent Hypertension

Session Information

• Hypertension and CVD: Mechanisms - I
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1403 Hypertension and CVD: Mechanisms

Authors

• Hara, Hiroaki, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Hiroaki Hara,

• Takayanagi, Kaori, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Kaori Takayanagi,

• Kitamura, Yuka, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Yuka Kitamura,

• Iwashita, Takatsugu, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Takatsugu Iwashita,

• Shimizu, Taisuke, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Taisuke Shimizu,

• Terao, Masaaki, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Masaaki Terao,

• Yamamoto, Ryo, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Ryo Yamamoto,

• Okada, Yoshimi, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Yoshimi Okada,

• Ogawa, Tomonari, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Tomonari Ogawa,

• Kanozawa, Koichi, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Koichi Kanozawa,

• Hasegawa, Hajime, School of Medicine, Saitama Medical University, Kawagoe, SAITAMA, Japan

Hajime Hasegawa,

Group or Team Name

• Department of Nephrology & Hypertension, Saitama Medical Center, Saitama Medical University

Background

Excessive intake of fructose causes a variety of adverse conditions including obesity, hepatic steatosis, insulin resistance, uric acid overproduction and hypertension which is the most common and significant pathological setting. Cause of the hypertension is not known at present. This study aimed to elucidate the underlying mechanism of fructose-induced hypertension by rat model.

Methods

Male SD rats (7 weeks old) were fed by food containing 60% glucose (GLU) and 60% fructose (FRU) for 3, 6 and 12 weeks. Histological, immunohistological and molecular biological analysis, and gene chip study were applied. No difference of calorie and salt intake of individual animal was daily checked by the measured weight of remaining food.

Results

Mean blood pressure and fractional sodium excretion (FENa) of FRU were both significantly higher (BP 12w-GLU: 94.8±3.4 vs 12w-FRU: 103.7±1.2 mmHg; FENa 12w-GLU: 0.084±0.011 vs 12w-FRU: 0.059±0.08%), suggesting that fructose caused ECF volume-dependent hypertension. Glomerular expansion in FRU (glomerular surface area in 12w-GLU: 7495±181 vs 12w-FRU: 9831±164 μm2) was agreed with the increase in the ECF volume. The expression of GLUT-5, fructose entry pathway, and ketohexokinase, phosphatase of fructose, in the proximal tubule were both up-regulated by fructose. As a candidate of fructose-induced salt reabsorption pathway, NHE3 was focused first because it is principal salt reabsorption pathway of proximal tubule. However, gene expression analysis, immunohistochemistry and immunoblotting of whole and phosphorylated NHE3 indicated negative results. To explore salt transporting molecules responding to fructose, gene chip analysis was conducted, and Slc5a10, corresponding to SGLT-5, showed significant up-regulation. The result was confirmed by RT-PCR (12w-GLU: 75.0±5.8% vs 12w-FLU: 230.1±16.0%), and SGLT-1 mRNA was also confirmed to be up-regulated (12w-GLU: 127.9±15.1% vs 12w-FLU: 214.8 ±37.4%).

Conclusion

Excess intake of fructose caused volume-dependent hypertension due to increased salt reabsorption through fructose-induced up-regulation of SGLT-1 and 5.