Program

OR30-4

Renal denervation inhibits high salt-induced body weight loss independently of urinary sodium excretion

[Speaker] Daisuke Yamazaki:1
[Co-author] Kento Kitada:2, Norihiko Morisawa:1,3, Yoshihide Fujisawa:4, Daisuke Nakano:1, Hirofumi Hitomi:1, Jens Titze:2,5, Akira Nishiyama:1
1:Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan, 2:Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, 3:Division of Nephrology & Hypertension, Department of Internal Medicine, Jikei School of Medicine, Tokyo, Japan, 4:Life Science Research Center, Faculty of Medicine, Kagawa University, Kagawa, Japan, 5:Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA

Introduction
We recently found that urea osmolytes are accumulated in the kidney to induce water reabsorption and concentrate salt into the urine when excess dietary salt is excreted in the urine. This renal sodium concentration process requires the energy-intensive nature of hepatic urea osmolyte production and leads to energy deficit and induces body weight loss with muscle protein wasting. Previous basic and clinical studies reported that renal denervation ameliorates hypertension and metabolic disorders such as insulin resistance. In this study, we hypothesized that renal denervation induces changes in energy metabolism, resulting in a prevention of high salt-induced body weight loss in mice.

Methods
We fed renal denervated or sham-operated male C57/B6J mice a 0.3% NaCl normal salt diet with tap water (NS + tap) or a 4% NaCl high salt diet with 0.9% saline to drink (HS + saline) for 4 consecutive weeks (ad libitum), followed by 2 weeks of pair-feeding to match energy intake in all groups. We measured daily food intake and body weight, 24 hours urinary sodium excretion, and liver arginase activity to examine hepatic urea production.

Results
In the sham-operated mice, HS + saline increased food intake without changing their body weight during ad libitum feeding and decreased the body weight during pair feeding compared to NS + tap, confirming the high salt-induced catabolism. Meanwhile, HS + saline mice did not show an increase in food intake during ad libitum and decrease in body weight during pair feeding in the renal denervated mice, suggesting that renal denervation prevents the high salt-induced body weight loss. In addition, HS + saline significantly increased the liver arginase activity in the sham group but not in the renal denervation group. Renal denervated mice did not show any increase in 24 hours urinary sodium excretion compared with sham-operated mice in both of NS + tap and HS + saline group.

Conclusion
These findings suggest that renal denervation prevents the high salt-induced body weight loss and hepatic urea production. The renal sympathetic nervous system could affect osmolyte and body fluid balance via changes in hepatic urea metabolism independently of urinary sodium excretion.

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