Water Intake In Mice Research Articles

Study on administration of 1,5-anhydro-D-fructose in C57BL/6J mice challenged with high-fat diet

1,5-Anhydro-D-fructose (AF) is a mono-saccharide directly formed from starch and glycogen by the action of α-1,4-glucan lyase (EC 4.2.2.13). Our previous study has indicated that AF increases glucose tolerance and insulin secretion in NMRI mice after administration through a gastric gavage in a single dose at 150 mg per mouse. In this study, we used high-fat feeding of C57BL/6J mice to examine the influence of long-term administration of AF on glucose-stimulated insulin secretion in vivo and in vitro. We found that 8-weeks of high-fat feeding increased body weight, fasting blood glucose and insulin levels in C57BL/6J mice when compared to mice fed normal diet. Impaired glucose tolerance was also observed in mice receiving 8-weeks of high-fat diet. In contrast, AF (1.5 g/kg/day), administered through drinking water for 8-weeks, did not affect body weight or food and water intake in mice fed either the high-fat or normal diet. There was no difference in basal blood glucose or insulin levels between AF-treated and control group. Oral glucose tolerance test (OGTT) showed that AF did not affect glucose-stimulated insulin secretion in mice. In in vitro studies with isolated islets, AF did not influence glucose-stimulated insulin secretion in mice receiving either high-fat or normal diet. We therefore conclude that when given through drinking water for 8 weeks at 1.5 g/kg/day, AF has no effect on glucose-stimulated insulin secretion in C57BL/6J mice challenged with a high-fat diet.

Central administration of obestatin fails to show inhibitory effects on food and water intake in mice

Obestatin is a ghrelin-associated peptide hormone with presumed anorexigenic and inhibitory effect on gastric propulsive motility activity. Recent literature, however, discloses much contestation over satiety and gastrointestinal motility-related functionalities of obestatin. In addition, antidipsinogenic effects in rodents by obestatin were recently reported. The present study was set up to bring more clarity into the contested effects of obestatin on food and water intake. Additionally, the stability of obestatin in brain tissue homogenate was investigated. The in vitro incubation of obestatin in brain homogenates revealed disappearance half-life times of 19 min for crude brain homogenate to 27 min for brain membrane homogenate. For the behavioural studies, male C57Bl/6 mice were intracerebroventricularly treated with 0.2 nmol murine amidated obestatin or vehicle at the age of 3 months. An additional group of mice was treated with 0.3 nmol of corticotropin releasing factor (CRF) as a positive control of suppression of food intake. Food and water intake were studied over a period of 5 h in metabolic cages. Under our experimental conditions, no suppressive effects of obestatin on food or water intake were observed, whereas CRF evoked a significant suppression of food intake, which proves the internal validity of the study design.

Structural modifications into diphenyl diselenide molecule do not cause toxicity in mice

The aim of the present study was to evaluate toxicological parameters of following compounds: 1a (4,4′-dichloro-diphenyl diselenide [(ClPhSe) 2]), 1b (3,3′-ditrifluoromethyl-diphenyl diselenide [(F 3CPhSe) 2]) and 1c (4,4′-dimethoxyl-diphenyl diselenide [(CH 3OPhSe) 2]). Calculated lethal dose (LD 50) values for mice exposed, by oral route, to a single application of compounds 1a, 1b or 1c were estimated to be >381, 278 and >372 mg/kg, respectively. Compounds 1a and 1b significantly reduced body weight gain as well as food and water intake in mice. δ-Aminolevulinate dehydratase (δ-ALA-D) and catalase activities were inhibited in mice which received the highest dose of compounds 1a or 1b. Exposure to compounds 1a, 1b and 1c did not modify lipid peroxidation, vitamin C levels, cerebral Na +/K +-ATPase activity and the biochemical parameters evaluated. The important point for medicinal chemistry is that the structural modifications are not introducing toxicity for the compounds in mice.

Effects of high potassium chloride supplementation on growth rate and renal function in mice

ABSTRACTFifty‐four mice were assigned to a control diet group or a KCl diet group to clarify the effects of KCl supplementation on growth rate, water intake and renal function in mice, and 5% of KCl was supplemented in KCl diets for 1–4 weeks. Bodyweights of KCl supplemented mice were significantly lower than those of control mice, and bodyweights of control and KCl supplemented mice at 28 days after treatment were 45.5 and 41.2 g, respectively. Feed intake was not affected by KCl supplementation, but water intake of KCl supplemented mice was significantly higher than that of control mice. Bone weights of KCl supplemented mice at 2 weeks after treatment were significantly lower than those of control mice. Serum urea nitrogen concentration at 4 weeks and serum K and Cl concentrations at 2 weeks were significantly lower in KCl supplemented mice. Histological alteration using hematoxylin–eosin and Sirius red staining was not found in the kidney of each mouse at 1, 2, and 4 weeks after treatment. These results suggest that high KCl supplementation decreases the rate of bodyweight gain and increases water intake in mice.

Role of angiotensin in body fluid homeostasis of mice: effect of losartan on water and NaCl intakes

It is known that mice injected peripherally with ANG II do not show a drinking response but that cFos immunoreactivity (ir) is induced in brain regions similar to those in rats. We now show in Crl:CD1(ICR) mice that peripheral injection of the ANG II type 1 receptor antagonist losartan was sufficient to prevent this induction of Fos-ir in the subfornical organ (SFO). Injection of ANG II into the lateral cerebral ventricle produced a robust water intake in mice and induced Fos-ir in SFO, as well as in median preoptic (MnPO) and paraventricular (PVN) nuclei. Peripheral injection of losartan blocked this drinking response and prevented the induction of Fos-ir in each of these brain regions. Hypovolemia produced by polyethylene glycol (PEG) produced a robust water intake but no evidence of sodium appetite, and it induced Fos-ir in SFO, MnPO, and PVN. Peripheral injection of losartan did not affect this drinking response. Fos-ir induced by PEG in SFO and MnPO was reduced by treatment with losartan, while that induced in the PVN was further increased by losartan. Sodium depletion with furosemide and low-sodium diet produced a strong sodium appetite and induced Fos-ir in SFO and MnPO. Treatment with losartan completely blocked the sodium appetite, as well as the induction of Fos-ir in these brain regions. These data indicate that endogenous production of ANG II and action at forebrain receptors is critically involved in depletion-related sodium appetite in mice. The absence of an effect of losartan on PEG-induced drinking suggests the critical involvement of other factor(s) such as arterial or venous baroreceptor input, and we discuss how this factor could also explain why peripheral ANG II is not dipsogenic in mice.

Studies of mannose metabolism and effects of long-term mannose ingestion in the mouse

Dietary mannose is used to treat glycosylation deficient patients with mutations in phosphomannose isomerase (PMI), but there is little information on mannose metabolism in model systems. We chose the mouse as a vertebrate model. Intravenous injection of [2- 3H]mannose shows rapid equilibration with the extravascular pool and clearance t 1/2 of 28 min with 95% of the label catabolized via glycolysis in <2 h. Labeled glycoproteins appear in the plasma after 30 min and increase over 3 h. Various organs incorporate [2- 3H]mannose into glycoproteins with similar kinetics, indicating direct transport and utilization. Liver and intestine incorporate most of the label (75%), and the majority of the liver-derived proteins eventually appear in plasma. [2- 3H]Mannose-labeled liver and intestine organ cultures secrete the majority of their labeled proteins. We also studied the long-term effects of mannose supplementation in the drinking water. It did not cause bloating, diarrhea, abnormal behavior, weight gain or loss, or increase in hemoglobin glycation. Organ weights, histology, litter size, and growth of pups were normal. Water intake of mice given 20% mannose in their water was reduced to half compared to other groups. Mannose in blood increased up to 9-fold (from 100 to 900 μM) and mannose in milk up to 7-fold (from 75 to 500 μM). [2- 3H]Mannose clearance, organ distribution, and uptake kinetics and hexose content of glycoproteins in organs were similar in mannose-supplemented and non-supplemented mice. Mannose supplements had little effect on the specific activity of phosphomannomutase (Man-6-P↔Man-1-P) in different organs, but specific activity of PMI in brain, intestine, muscle, heart and lung gradually increased <2-fold with increasing mannose intake. Thus, long-term mannose supplementation does not appear to have adverse effects on mannose metabolism and mice safely tolerate increased mannose with no apparent ill effects.

The effect of adrenocorticotrophic hormone on water intake in mice

The systemic administration of adrenocorticotrophic hormone (ACTH) stimulates the intake of sodium chloride and water in many species. In mice the daily intake of water may reach half of the total body water content. To establish whether this very high water intake was primary or secondary to the sodium chloride intake, Synacthen was infused SC at 2.8 μg/day by Alzet miniosmotic pump to mice that did not have access to sodium chloride solution. On low-sodium food, the daily water intake increased from 2.99 ± 0.08 ml (mean ± SEM) to 9.85 ± 0.74 ml ( p < 0.05, n = 6) by day 7 of infusion and remained significantly higher than the control value until the fourth postinfusion day. On high-sodium food, the daily water intake also increased 350% from a higher baseline, 4.55 ± 0.14 ml, and returned to the control value by the second postinfusion day. The same ACTH treatment for 4 days increased plasma [Na] and appeared to expand plasma volume. The results show that a high water intake caused by ACTH administration in mice is not secondary to a concurrent increase in sodium chloride intake. The water intake may be induced by stimulation of the secretion of adrenal steroid hormones which increase plasma [Na].

A sex difference in the effect of CCK-8 on food and water intake in obese (ob/ob) and lean (+/+) mice

Male and female ob/ob and +/+ mice were tested with CCK-8 (1, 2, 4 and 8 μg/kg) administered 15 min prior to 30-min access to solid food after 17.5 hr food deprivation and 15 min prior to 30-min access to water after 17.5 hr water deprivation. The threshold dose for suppressing 30-min food intake was 2 μg/kg for all mice. Larger doses of CCK-8 inhibited food intake in male obese and lean mice in a linear fashion. The dose-response relationship for female mice, however, was not linear: lean females failed to suppress food intake following 4 or 8 μg/kg and obese females did not suppress food intake at 4 μg/kg. There was also a sex difference in the effect on water intake. No dose of CCK-8 changed water intake in lean males and only the 8 μg/kg dose decreased water intake in obese males. In contrast CCK-8 (1, 4 and 8 μg/kg) increased water intake in obese females, CCK-8 (1 and 8 μg/kg) increased water intake in lean females and no dose of CCK-8 decreased water intake in females. These data demonstrate significant sex differences in the effect of CCK-8 on food and water intake in mice.

Effects of N-nitrosopyrrolidine, nitrite and pyrrolidine on tumour development in mice as related to ingestion of cured meat

The incidence of tumours in mice fed a standard chow diet and given either N-nitrosopyrrolidine (NPyr), nitrite (NO 2) or nitrite plus pyrrolidine (NO 2 + Pyr) in the drinking water for 12 months at 100mg, 1 g and 1 g plus 100mg/litre, respectively, was compared with that for a control group (C) receiving no additives. Differences between groups in weight gain and feed consumption were not significant. Group 3 (NO 2) drank less water ( P < 0·05) than those in groups 1 (C) and 2 (NPyr). Water intake of mice in group 4 (NO 2 + Pyr) did not differ from that of any of the other three groups. Survival rates were: 94% (C), 80% (NPyr), 92% (NO 2) and 83% (NO 2 + Pyr); but the differences were not statistically significant. Gross examination upon autopsy revealed that the incidence of all tumours in group 2 (NPyr) was 10- to 20-fold higher than that in any other group. Histological examination confirmed that NPyr induced more ( P < 0.05) malignant tumours in liver and lungs with any other treatment; otherwise there were no significant differences. Results indicated that NO 2 + Pyr (nitrite plus a secondary amine) did not increase the frequency of carcinogenic tumours in mice.

Rhythm of water intake of mice in the daytime under continuous darkness.

Rhythm of water intake of mice in the daytime under continuous darkness.

Relationship of food and water intake in aurothioglucose obesity.

After ld50 doses of aurothioglucose (ATG), extensive damage to hypothalamic structures other than those strictly involved in food intake has been demonstrated. The injury to areas previously shown to be concerned with the regulation of water intake prompted an investigation of the daily patterns of food and water intake in mice from the 2nd day after ATG injection for a period of 6 months. During the 1st month after ATG no statistically significant differences were noted in food or water intake or water-to-food ratios among mice destined to become obese, ATG-nonobese mice, or controls. From the 2nd to 6th month statistically significant increases in food and water intake were demonstrated among obese mice compared to ATG-nonobese and control mice. At no time after the injection of ATG was there a demonstrable difference in water-to-food ratios among the three groups. It is concluded that alteration of water intake regulatory mechanisms is not a concomitant of aurothioglucose obesity.