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
This is a preview of subscription content, log in to check access.
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.
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).
Westerterp KR, Plasqui G, Goris AH (2005) Water loss as a function of energy intake, physical activity and season. Br J Nutr 93:199–203CrossRefGoogle Scholar
Jequier E, Constant F (2010) Water as an essential nutrient: the physiological basis of hydration. Eur J Clin Nutr 64:115–123CrossRefGoogle Scholar
Armstrong LE, Johnson EC, McKenzie AL, Munoz CX (2016) An empirical method to determine inadequacy of dietary water. Nutrition 32:79–82CrossRefGoogle Scholar
Nakamura K, Velho G, Bouby N (2017) Vasopressin and metabolic disorders: translation from experimental models to clinical use. J Intern Med 282:298–309CrossRefGoogle Scholar
Feehally J, Khosravi M (2015) Effects of acute and chronic hypohydration on kidney health and function. Nutr Rev 73(Suppl 2):110–119CrossRefGoogle Scholar
MacManes MD (2017) Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury. Am J Physiol Renal Physiol 313:F262–F272CrossRefGoogle Scholar
Scrogin KE, Grygielko ET, Brooks VL (1999) Osmolality: a physiological long-term regulator of lumbar sympathetic nerve activity and arterial pressure. Am J Physiol 276:R1579–R1586Google Scholar
Melander O (2016) Vasopressin, from regulator to disease predictor for diabetes and cardiometabolic risk. Ann Nutr Metab 68(Suppl 2):24–28CrossRefGoogle Scholar
Woolsey CA, Coopersmith CM (2006) Vasoactive drugs and the gut: is there anything new? Curr Opin Crit Care 12:155–159CrossRefGoogle Scholar
Heinsen FA, Fangmann D, Muller N, Schulte DM, Ruhlemann MC, Turk K et al (2016) Beneficial effects of a dietary weight loss intervention on human gut microbiome diversity and metabolism are not sustained during weight maintenance. Obes Facts 9:379–391CrossRefGoogle Scholar
Kaska L, Sledzinski T, Chomiczewska A, Dettlaff-Pokora A, Swierczynski J (2016) Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome. World J Gastroenterol 22:8698–8719CrossRefGoogle Scholar
Leenen FH, de Jong W (1981) Hypotensive effect of water restriction in the two-kidney one-clip hypertensive rat. Am J Physiol 241:F525–F531Google Scholar
Hilliard LM, Colafella KMM, Bulmer LL, Puelles VG, Singh RR, Ow CPC et al (2016) Chronic recurrent dehydration associated with periodic water intake exacerbates hypertension and promotes renal damage in male spontaneously hypertensive rats. Sci Rep 6:33855CrossRefGoogle Scholar
Park F, Koike G, Cowley AW Jr (1998) Regional time-dependent changes in vasopressin V2 receptor expression in the rat kidney during water restriction. Am J Physiol 274:F906–F913Google Scholar
Chang T, Ravi N, Plegue MA, Sonneville KR, Davis MM (2016) Inadequate hydration, BMI, and obesity among US adults: NHANES 2009-2012. Ann Fam Med 14:320–324CrossRefGoogle Scholar
Thornton SN (2016) Increased hydration can be associated with weight loss. Front Nutr 3:18CrossRefGoogle Scholar
Milla-Tobarra M, Garcia-Hermoso A, Lahoz-Garcia N, Notario-Pacheco B, Lucas-de la Cruz L, Pozuelo-Carrascosa DP et al (2016) The association between water intake, body composition and cardiometabolic factors among children—the Cuenca study. Nutr Hosp 33:312CrossRefGoogle Scholar
Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951CrossRefGoogle Scholar
Niwa H, Ogawa Y, Kido Y, Abe Y, Kobayashi M, Mori T et al (1989) The rate of lipid oxidation in septic rat models. Jpn J Surg 19:439–445CrossRefGoogle Scholar
Even PC, Nadkarni NA (2012) Indirect calorimetry in laboratory mice and rats: principles, practical considerations, interpretation and perspectives. Am J Physiol Regul Integr Comp Physiol 303:R459–R476CrossRefGoogle Scholar
Yang HJ, Kwon DY, Kim MJ, Kim DS, Kang S, Shin BK et al (2014) Red peppers with different pungencies and bioactive compounds differentially modulate energy and glucose metabolism in ovariectomized rats fed high fat diets. J Funct Foods 7:246–256CrossRefGoogle Scholar
Park S, da Kim S, Kang S (2011) Gastrodia elata Blume water extracts improve insulin resistance by decreasing body fat in diet-induced obese rats: vanillin and 4-hydroxybenzaldehyde are the bioactive candidates. Eur J Nutr 50:107–118CrossRefGoogle Scholar
Park S, Kim DS, Kang S (2016) Vitamin D deficiency impairs glucose-stimulated insulin secretion and increases insulin resistance by reducing PPAR-gamma expression in nonobese type 2 diabetic rats. J Nutr Biochem 27:257–265CrossRefGoogle Scholar
Yang HJ, Kim MJ, Kwon DY, Moon BR, Kim AR, Kang S et al (2016) The combination of Artemisia princeps Pamp, Leonurus japonicas Houtt, and Gardenia jasminoides Ellis fruit attenuates the exacerbation of energy, lipid, and glucose by increasing hepatic PGC-1alpha expression in estrogen-deficient rats. BMC Complement Altern Med 16:137CrossRefGoogle Scholar
Zhou X, Burg MB, Ferraris JD (2012) Water restriction increases renal inner medullary manganese superoxide dismutase (MnSOD). Am J Physiol Renal Physiol 303:F674–F680CrossRefGoogle Scholar
Park S, Kim DS, Kang S, Shin BK (2015) Synergistic topical application of salt-processed Phellodendron amurense and Sanguisorba officinalis Linne alleviates atopic dermatitis symptoms by reducing levels of immunoglobulin E and pro-inflammatory cytokines in NC/Nga mice. Mol Med Rep 12:7657–7664CrossRefGoogle Scholar
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408CrossRefGoogle Scholar
Park S, Hong SM, Lee JE (1985) Sung SR (2007) Exercise improves glucose homeostasis that has been impaired by a high-fat diet by potentiating pancreatic beta-cell function and mass through IRS2 in diabetic rats. J Appl Physiol 103:1764–1771CrossRefGoogle Scholar
Goodrich JK, Di Rienzi SC, Poole AC, Koren O, Walters WA, Caporaso JG et al (2014) Conducting a microbiome study. Cell 158:250–262CrossRefGoogle Scholar
Rieg TS, Doerries LE, O’Shea JG, Aravich PF (1993) Water deprivation produces an exercise-induced weight loss phenomenon in the rat. Physiol Behav 53:607–610CrossRefGoogle Scholar
Ruginsk SG, Vechiato FM, Uchoa ET, Elias LL, Antunes-Rodrigues J (2015) Type 1 cannabinoid receptor modulates water deprivation-induced homeostatic responses. Am J Physiol Regul Integr Comp Physiol 309:R1358–R1368CrossRefGoogle Scholar
Donald JA, Hamid NK, McLeod JL (2017) The role of leptin and ghrelin in appetite regulation in the Australian Spinifex hopping mouse, Notomys alexis, during long-term water deprivation. Gen Comp Endocrinol 244:201–208CrossRefGoogle Scholar
Davis RAH, Halbrooks JE, Watkins EE, Fisher G, Hunter GR, Nagy TR et al (2017) High-intensity interval training and calorie restriction promote remodeling of glucose and lipid metabolism in diet-induced obesity. Am J Physiol Endocrinol Metab 313:E243–E256CrossRefGoogle Scholar
Pires RC, Souza EE, Vanzela EC, Ribeiro RA, Silva-Santos JC, Carneiro EM et al (2014) Short-term calorie restriction improves glucose homeostasis in old rats: involvement of AMPK. Appl Physiol Nutr Metab 39:895–901CrossRefGoogle Scholar
Campbell NR, Wickert W, Magner P, Shumak SL (1994) Dehydration during fasting increases serum lipids and lipoproteins. Clin Invest Med 17:570–576Google Scholar
Amaral ME, Ribeiro RA, Vanzela EC, Barbosa-Sampaio HC (2016) Reduced AMPKalpha2 protein expression restores glucose-induced insulin secretion in islets from calorie-restricted rats. Int J Exp Pathol 97:50–55CrossRefGoogle Scholar
Malandrucco I, Pasqualetti P, Giordani I, Manfellotto D, De Marco F, Alegiani F et al (2012) Very-low-calorie diet: a quick therapeutic tool to improve beta cell function in morbidly obese patients with type 2 diabetes. Am J Clin Nutr 95:609–613CrossRefGoogle Scholar
Seganfredo FB, Blume CA, Moehlecke M, Giongo A, Casagrande DS, Spolidoro JVN et al (2017) Weight-loss interventions and gut microbiota changes in overweight and obese patients: a systematic review. Obes Rev 18:832–851CrossRefGoogle Scholar
Ruiz A, Cerdo T, Jauregui R, Pieper DH, Marcos A, Clemente A et al (2017) One-year calorie restriction impacts gut microbial composition but not its metabolic performance in obese adolescents. Environ Microbiol 19:1536–1551CrossRefGoogle Scholar
Pan F, Zhang L, Li M, Hu Y, Zeng B, Yuan H et al (2018) Predominant gut Lactobacillus murinus strain mediates anti-inflammation effects in calorie-restricted mice. Microbiome 6:54CrossRefGoogle Scholar