Chronic water insufficiency induced kidney damage and energy dysregulation despite reduced food intake, which improved gut microbiota in female rats

  • James W. Daily
  • Ting Zhang
  • Xuangao Wu
  • Sunmin ParkEmail author
Original Paper


Water intake is recommended for weight loss, but the relationship between water intake and energy metabolism is not clear. We hypothesized that long-term water insufficiency would influence energy, glucose, and lipid metabolism while modulating gut microbiota. Female rats were provided with high-fat diets with different amounts of water and food intake for 6 weeks as follows: water provided for 1 h per day with food ad libitum (WRFA), water supply ad libitum plus pair feeding of with water restricted rats(WAFR), water restriction with ad libitum food for 3 weeks and water and food intake ad libitum for 3 weeks (WR-WA) and ad libitum supply of water and food (WAFA). Water intake in WRFA was about one-third of WAFR and WAFA, whereas food intake was lowered by 30% in WRFA and WAFR than WAFA. Body fat decreased in WRFA and WAFR, but WAFR decreased fat mass more than WRFA. Energy expenditure was lower in WRFA than WAFA and carbohydrate utilization was much higher in WRFA than the other groups. The peak serum glucose concentrations were lower in WAFA than the other groups and WRFA lowered serum insulin levels more than WAFA during OGTT. WRFA shrank the glomerulus with increased apoptotic cells and damaged renal tubules compared to the WAFA and WAFR. WR-WA also exhibited greater glomerular shrinkage and apoptosis that WAFA, but not as much WRFA, indicating that the kidneys were healing after water restriction damage. WRFA exacerbated dyslipidemia compared to the WAFA and WAFR groups. The gut microbiome was similarly modulated in WRFA and WAFR, compared to WAFA, but it was mainly affected by food intake, not water restriction in the host. WRFA and WAFR increased Bacteroidetes and decreased Firmicutes compared WAFA. In conclusion, chronic insufficient water intake induced renal damage, decreased energy expenditure, and exacerbated dyslipidemia in rats with reduced food intake. However, the reduction of food intake improved gut microbiome regardless of insufficient water intake and only minor effects on the microbiome were observed due to water restriction.


Water deprivation Insulin Glucose Energy expenditure Gut microbiota 


Author contributions

JWD and SP designed the research. XW and TZ performed animal experiments. SP performed statistical analyses. JWD and SP drafted the article. All authors discussed the results and implications and commented on the manuscript at all stages. All authors contributed to the writing and editing of the article.


This research was supported by the Academic Research Fund of Hoseo University in 2017 (2017-0103).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

All experimental procedures were conducted according to the Guide for the Care, and Use of Laboratory Animals from the National Institutes of Health (NIH) and were approved by the Institutional Animal Care and Use Committee of Hoseo University (HUACUC-17-47).


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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.R&D, Daily ManufacturingRockwellUSA
  2. 2.Department of Food and Nutrition, Obesity/Diabetes CenterHoseo UniversityAsanSouth Korea

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