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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2006-1438
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The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 8 3334-3337
Copyright © 2007 by The Endocrine Society

BRIEF REPORT

Water Drinking Induces Thermogenesis through Osmosensitive Mechanisms

Michael Boschmann, Jochen Steiniger, Gabriele Franke, Andreas L. Birkenfeld, Friedrich C. Luft and Jens Jordan

Franz-Volhard Clinical Research Center and Helios-Klinikum-Berlin, Charité Campus Buch, Universitary Medicine Berlin, D-13125 Berlin, Germany

Address all correspondence and requests for reprints to: Jens Jordan, M.D., Franz Volhard Clinical Research Center, Charité Campus Buch, Universitary Medicine Berlin, Wiltbergstrasse 50, Hs. 129, D-13125 Berlin, Germany. E-mail: jens.jordan{at}charite.de.


   Abstract
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 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: Recently, we showed that drinking 500 ml water induces thermogenesis in normal-weight men and women.

Objective: We now repeated these studies in a randomized, controlled, crossover trial in overweight or obese otherwise healthy subjects (eight men and eight women), comparing also the effects of 500 ml isoosmotic saline or 50 ml water.

Results: Only 500 ml water increased energy expenditure by 24% over the course of 60 min after ingestion, whereas isoosmotic saline and 50 ml water had no effect. Heart rate and blood pressure did not change in these young, healthy subjects.

Conclusions: Our data exclude volume-related effects or gastric distension as the mediator of the thermogenic response to water drinking. Instead, we hypothesize the existence of a portal osmoreceptor, most likely an ion channel.


   Introduction
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 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
EXTRACELLULAR HYPEROSMOLARITY causes cell shrinkage, whereas extracellular hypoosmolarity causes cell swelling. Osmotically induced cell volume changes modulate important cellular functions, both in vitro and in vivo, which may influence the organism directly or indirectly through homeostatic reflex pathways (1, 2). Subtle changes in osmolarity occur in daily life even in healthy people. For example, water drinking changes osmolarity in the portal circulation (2) and also acutely activates the sympathetic nervous system (3, 4). Indeed, water drinking raises both plasma norepinephrine concentrations and muscle sympathetic nerve activity (3, 4, 5). The sympathetic activation drives a profound pressor response in autonomic failure patients (4, 6). The response is abolished with pharmacological ganglionic blockade (4). Moreover, metabolic rate increases almost 30% in healthy, normal-weight subjects (7). The response is attenuated with ß-adrenoreceptor blockade (7). Only one third of the increase in metabolic rate was explained by the energy demand to warm the water from 22 C to body temperature. The metabolic response was attenuated with systemic ß-adrenoreceptor blockade (7). The increase in metabolic rate was not reproduced in a recent study using a different methodology (8). Cardiovascular sympathetic responses were elicited by water but not saline, thereby implicating osmosensitive mechanisms (5, 9, 10). The objective of our study was to test whether water drinking elicits the same thermogenic response in obese as in normal-weight subjects and whether it is related to gastrointestinal distention, hypoosmotic stimulation, or both.


   Subjects and Methods
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 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
We studied overweight or obese otherwise healthy subjects on no medications [eight men, age 29 ± 2 (range 20–42) yr, body mass index (BMI) 33 ± 1.3 (range 29–39) kg/m2; eight women, age 33 ± 2 (range 27–39) yr, BMI 30.3 ± 0.4 (range 29–32) kg/m2]. The institutional review board approved all studies. Written informed consent was obtained before study entry.

All subjects included in our study had a sedentary lifestyle. Nevertheless, we asked our subjects to abstain from strenuous physical exercise 48 h before testing. Furthermore, subjects were asked to abstain from smoking and consuming alcoholic drinks and caffeine-containing beverages or snacks 48 h before testing. They were also advised to take a light dinner no later than 13 h before testing. Subjects did not eat 12.5 h and did not drink 1.5 h before testing. They appeared in our laboratory at 0830 h. Testing was begun at 0900 h after they had emptied the bladder. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured by using a respiratory chamber, considering the methodological improvements introduced by Brown et al. (11), to assess changes in energy expenditure and respiratory quotient (RQ = VCO2/VO2). The respiratory chamber had a volume of 5800 liters and was calibrated with acetone burning. In earlier tests, we confirmed that the respiratory chamber was able to follow rapid changes in metabolic rate. When using 20-min integration periods, the time course of the postprandial thermogenic response after ingesting a standardized test meal was virtually identical over 360 min with the respiratory chamber and a canopy system, respectively (n = 6). We measured heart rate and brachial blood pressure every 5 min (Dinamap). Subjects remained seated throughout the experiment and were continuously monitored through a window in the metabolic chamber. After a run-in period of 15 min, resting energy expenditure was determined for 30 min. Thereafter, the subjects ingested 50 ml (control) or 500 ml tap water (pH 7.5; [Na+] 1.5 mmol/liter; [Ca2+] 3.1 mmol/liter) or 500 ml isoosmotic saline in less than 5 min. Testing was conducted on separate days in a randomized, crossover fashion such that each subject was tested with all fluids. Temperature of the fluids was 22 C. After completion of drinking, measurements were continued for another 90 min.

Energy expenditure was calculated according to Ferrannini (12). All data are given as means ± SEM. ANOVA with repeated measures was used followed by post tests. A value for P < 0.05 was considered statistically significant.


   Results
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 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Resting energy expenditure was 5.66 ± 0.25 kJ/min before 500 ml water, 5.62 ± 0.25 kJ/min before saline, and 5.68 ± 0.24 kJ/min before 50 ml water drinking (not significant). Within 10 min after drinking 500 ml water, energy expenditure started to increase, reaching a maximum of 24 ± 3% above baseline after 60 min (Fig. 1Go, top). The response to 500 ml water was significantly greater than the response to 50 ml water or to 500 ml saline (P < 0.0001 by ANOVA for both comparisons). We calculated the individual thermogenic response between 0 and 90 min after fluid ingestion (Fig. 1Go, bottom). On average, subjects used an additional 95 ± 10 kJ with 500 ml water, 28 ± 4.7 kJ with 50 ml water, and 43 ± 4.6 kJ with 500 ml saline (P < 0.0001 by ANOVA). Resting RQ was 0.81 ± 0.01 before drinking 500 ml water, 50 ml water, or 500 ml saline, and it did not change significantly over 60 min after drinking the test fluids. None of the interventions elicited blood pressure or heart rate changes (Fig. 2Go).


Figure 1
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  		FIG. 1. Top, Relative change in energy expenditure (EE) over time in obese subjects (eight men, eight women) after drinking 50 ml water (50 water), 500 ml water (500 water), or 500 ml isoosmotic saline (500 NaCl). At 0 min, subjects started to drink the fluids in less than 5 min. Testing was conducted in a randomized and crossover fashion on separate days. *, P < 0.05; **, P < 0.01, for the comparison between 500 ml water and 500 ml saline; #, P < 0.001 for the comparison between 500 and 50 ml water. Bottom, Individual thermogenic responses to 50 ml water, 500 ml water, or 500 ml normal saline. The response was calculated between 0 and 90 min after drinking. The dotted line indicates the energy that is required to heat 500 ml water or saline from room temperature to body temperature. The P values are given for the analysis with Bonferoni’s post test (PANOVA < 0.0001).

 

Figure 2
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  		FIG. 2. Changes in heart rate (HR) and systolic blood pressure (SBP) over time in obese subjects (eight men, eight women) before and after drinking 50 ml water (50 water), 500 ml water (500 water), or 500 ml isoosmotic saline (500 NaCl).

 

   Discussion
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 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Drinking water induces a much greater thermogenic response than drinking the same volume of isoosmotic saline. We do not have a good explanation why water drinking induced a thermogenic response in some but not in all studies (7, 8). In the present and in our previous study (7), we applied a metabolic chamber. Brown et al. (8) obtained measurements using a canopy system. It is difficult to explain the discrepant results with these methodological differences. Despite these issues, we suggest that our observation provides clues regarding the underlying mechanism of water-induced thermogenesis. We previously showed a gender difference in the substrates used for fueling water-induced thermogenesis (7). Water drinking increased lipid oxidation in men and carbohydrate oxidation in women. In obese subjects, the response to water appears to be more uniform, i.e. RQ did not change significantly in men and women, indicating no change in the ratio between carbohydrate and lipid oxidation rate. We speculate that obese subjects may be less able to switch between carbohydrate and lipid oxidation; the phenomenon is sometimes referred to as metabolic inflexibility.

Similarly to previous studies (3, 4), water drinking did not elicit a pressor response in younger subjects without autonomic dysfunction. In contrast, water raises blood pressure in autonomic failure patients (4). Thus, intact autonomic cardiovascular regulation appears to attenuate the water-induced pressor response through baroreflex mechanisms. Similarly, low doses of the sympathetic stimulant yohimbine raise blood pressure in autonomic failure patients (4). The same doses change blood pressure little or not at all in healthy subjects.

The mechanism causing sympathetic activation with water drinking is not fully understood. Studies in tetraplegic patients suggest a spinal mechanism (13). The nature of the afferent stimulus and the afferent pathway causing activation of efferent sympathetic neurons is unknown. Water temperature, distention of gastrointestinal organs, or changes in osmolarity could be involved. Water-drinking-induced cardiovascular and metabolic responses are not solely explained by a thermal stimulus. In autonomic failure patients, drinking colder or warmer water elicited an identical pressor response (4). In healthy normal-weight subjects, approximately 60–70% of the water-induced thermogenesis could not be attributed to heating of the ingested water (7). Indeed, drinking 37 C warm water elicited a substantial thermogenic response (7). Gastric distention increases sympathetic nerve traffic in human subjects (14). We did not measure gastric distention directly. However, the differential response to drinking water or saline in our study suggests that gastric distention is not the crucial mechanism for water-drinking-induced sympathetic activation. The idea is supported by the observation that water drinking elicits more pronounced cardiovascular responses than drinking the same volume of saline (5, 9, 10). Similarly, in dogs, gastric water infusion elicited a much greater pressor response than isoosmotic saline in the same amounts or the inflation of a gastric balloon (2). Furthermore, human magnetic resonance imaging studies demonstrated that after 40 min, only 25% of the ingested water remains in the stomach (15).

The main difference between water and isoosmotic saline is the osmolarity of the solution. Water is hypoosmotic in contrast to isoosmotic saline. Thus, our data suggest that the water-induced changes may be explained by stimulation of osmosensitive structures. Indeed, the time course of the changes in sympathetic activity (3), blood pressure (4, 6, 13), and metabolic rate (7) parallel the time course of altered plasma osmolarity after water drinking (7). Moreover, infusion of hypoosmotic solutions through a gastric tube in humans caused a greater increase in sweat production, a sympathetic response, than infusion of isoosmotic solutions (2).

We suggest that water drinking induces a local decrease in osmolarity in the gastrointestinal tract, portal vein, and liver. A local decrease in extracellular osmolarity may influence thermogenesis through local changes in organ function, altered activity of osmosensitive neural pathways, or both mechanisms combined. Indeed, osmotic cell swelling activates anabolic processes including glycogen and protein synthesis in the presence of suitable substrates (16). Furthermore, the decrease in osmolarity may stimulate afferent neurons projecting to the spinal chord. Osmoreceptive afferent nerve fibers in the portal vein and in the liver have been identified in animals (17). Physiological studies provided additional evidence for existence of peripheral osmoreceptors (2). Although our study suggests that water-induced sympathetic activation may be secondary to stimulation of osmosensitive afferent neurons, the transduction mechanism is unknown. Serotonin, glutamine, and substance P release might be involved (18). Hypoosmolarity causes cell swelling and, therefore, membrane stretch. We hypothesize that osmosensory transduction may rely on stretch-sensitive ion channels. Members of the transient receptor potential (TRP) family, such as TRPV1 (19) or TRPV4 (20), are prime suspects.


   Footnotes
 
This work was supported by the Helmholtz Society and an unrestricted grant from Forum Trinkwasser e.V.

Author Disclosure: M.B., J.S., G.F., A.L.B., F.C.L., and J.J. have nothing to declare.

First Published Online May 22, 2007

Abbreviations: BMI, Body mass index; RQ, respiratory quotient; TRP, transient receptor potential.

Received July 5, 2006.

Accepted May 11, 2007.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Lang F, Busch GL, Ritter M, Volkl H, Waldegger S, Gulbins E, Haussinger D 1998 Functional significance of cell volume regulatory mechanisms. Physiol Rev 78:247–306[Abstract/Free Full Text]
  2. Haberich FJ 1968 Osmoreception in the portal circulation. Fed Proc 27:1137–1141[Medline]
  3. Scott EM, Greenwood JP, Gilbey SG, Stoker JB, Mary DA 2001 Water ingestion increases sympathetic vasoconstrictor discharge in normal human subjects. Clin Sci Colch 100:335–342[Medline]
  4. Jordan J, Shannon JR, Black BK, Ali Y, Farley M, Costa F, Diedrich A, Robertson RM, Biaggioni I, Robertson D 2000 The pressor response to water drinking in humans: a sympathetic reflex? Circulation 101:504–509[Abstract/Free Full Text]
  5. Raj SR, Biaggioni I, Black BK, Rali A, Jordan J, Taneja I, Harris PA, Robertson D 2006 Sodium paradoxically reduces the gastropressor response in patients with orthostatic hypotension. Hypertension 48:329–334[Abstract/Free Full Text]
  6. Jordan J, Shannon JR, Grogan E, Biaggioni I, Robertson D 1999 A potent pressor response elicited by drinking water. Lancet 353:723
  7. Boschmann M, Steiniger J, Hille U, Tank J, Adams F, Sharma AM, Klaus S, Luft FC, Jordan J 2003 Water-induced thermogenesis. J Clin Endocrinol Metab 88:6015–6019[Abstract/Free Full Text]
  8. Brown CM, Dulloo AG, Montani JP 2006 Water-induced thermogenesis reconsidered: the effects of osmolality and water temperature on energy expenditure after drinking. J Clin Endocrinol Metab 91:3598–3602[Abstract/Free Full Text]
  9. Lipp A, Tank J, Franke G, Arnold G, Luft FC, Jordan J 2005 Osmosensitive mechanisms contribute to the water drinking-induced pressor response in humans. Neurology 65:905–907[Abstract/Free Full Text]
  10. Brown CM, Barberini L, Dulloo AG, Montani JP 2005 Cardiovascular responses to water drinking: does osmolality play a role? Am J Physiol Regul Integr Comp Physiol 289:R1687–R1692
  11. Brown D, Cole TJ, Dauncey MJ, Marrs RW, Murgatroyd PR 1984 Analysis of gaseous exchange in open-circuit indirect calorimetry. Med Biol Eng Comput 22:333–338[CrossRef][Medline]
  12. Ferrannini E 1988 The theoretical bases of indirect calorimetry: a review. Metabolism 37:287–301[CrossRef][Medline]
  13. Tank J, Schroeder C, Stoffels M, Diedrich A, Sharma AM, Luft FC, Jordan J 2003 Pressor effect of water drinking in tetraplegic patients may be a spinal reflex. Hypertension 41:1234–1239[Abstract/Free Full Text]
  14. Rossi P, Andriesse GI, Oey PL, Wieneke GH, Roelofs JM, Akkermans LM 1998 Stomach distension increases efferent muscle sympathetic nerve activity and blood pressure in healthy humans. J Neurol Sci 161:148–155[CrossRef][Medline]
  15. Ploutz-Snyder L, Foley J, Ploutz-Snyder R, Kanaley J, Sagendorf K, Meyer R 1999 Gastric gas and fluid emptying assessed by magnetic resonance imaging. Eur J Appl Physiol Occup Physiol 79:212–220[CrossRef][Medline]
  16. Haussinger D 1996 The role of cellular hydration in the regulation of cell function. Biochem J 313(Pt 3):697–710
  17. Adachi A 1984 Thermosensitive and osmoreceptive afferent fibers in the hepatic branch of the vagus nerve. J Auton Nerv Syst 10:269–273[CrossRef][Medline]
  18. Wu XY, Zhu JX, Gao J, Owyang C, Li Y 2005 Neurochemical phenotype of vagal afferent neurons activated to express C-FOS in response to luminal stimulation in the rat. Neuroscience 130:757–767[CrossRef][Medline]
  19. Sharif NR, Witty MF, Seguela P, Bourque CW 2006 An N-terminal variant of Trpv1 channel is required for osmosensory transduction. Nat Neurosci 9:93–98[CrossRef][Medline]
  20. Alessandri-Haber N, Dina OA, Yeh JJ, Parada CA, Reichling DB, Levine JD 2004 Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat. J Neurosci 24:4444–4452[Abstract/Free Full Text]



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