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Quinine Controls Body Weight Gain Without Affecting Food Intake in Male C57BL6 Mice

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Quinine Controls Body Weight Gain Without Affecting Food Intake in Male C57BL6 Mice

Philippe Cettour-Rose et al. BMC Physiol.

Abstract

Background: Quinine is a natural molecule commonly used as a flavouring agent in tonic water. Diet supplementation with quinine leads to decreased body weight and food intake in rats. Quinine is an in vitro inhibitor of Trpm5, a cation channel expressed in taste bud cells, the gastrointestinal tract and pancreas. The objective of this work is to determine the effect of diet supplementation with quinine on body weight and body composition in male mice, to investigate its mechanism of action, and whether the effect is mediated through Trpm5.

Results: Compared with mice consuming AIN, a regular balanced diet, mice consuming AIN diet supplemented with 0.1% quinine gained less weight (2.89 ± 0.30 g vs 5.39 ± 0.50 g) and less fat mass (2.22 ± 0.26 g vs 4.33 ± 0.43 g) after 13 weeks of diet, and had lower blood glucose and plasma triglycerides. There was no difference in food intake between the mice consuming quinine supplemented diet and those consuming control diet. Trpm5 knockout mice gained less fat mass than wild-type mice. There was a trend for a diet-genotype interaction for body weight and body weight gain, with the effect of quinine less pronounced in the Trpm5 KO than in the WT background. Faecal weight, energy and lipid contents were higher in quinine fed mice compared to regular AIN fed mice and in Trpm5 KO mice compared to wild type mice.

Conclusion: Quinine contributes to weight control in male C57BL6 mice without affecting food intake. A partial contribution of Trpm5 to quinine dependent body weight control is suggested.

Figures

Figure 1
Figure 1
Body weight, fat and lean mass of WT mice on control diet, diet + 0.1% quinine, or diet + 0.01% quinine, showing lower body weight and fat mass gains with 0.1% quinine but not with 0.01% quinine, compared to regular diet. * p < 0.05, **p < 0.01, ***p < 0.001.
Figure 2
Figure 2
Food intake of WT mice on AIN diet with or without quinine. A. Cumulative food intake of mice on control AIN diet, AIN diet + 0.1% quinine, or AIN diet + 0.01 % quinine, showing no difference between any of the groups. B. Daily real food intake and food waste of wild type mice consuming AIN diet, or AIN diet supplemented with 0.1% or 0.01% quinine. Real food intake was calculated by subtracting waste from measured food intake. There is no significant difference between groups with different diets. There is a trend for increased real food intake by animals fed quinine supplemented diets. C. Diet preference tests, comparing AIN diet and AIN diet supplemented with either 0.01% or 0.1% quinine, showing aversion for the quinine supplemented diets.
Figure 3
Figure 3
Blood glucose, plasma insulin, triglycerides (TG), and free fatty acids (FFA) from 0.1% quinine fed (quinine) and control diet fed (control) WT mice, and from Trpm5 KO mice fed a control diet (KO) for blood glucose. Blood glucose is more elevated in the control than in quinine or Trpm5 KO mice. There is no difference in plasma insulin between control and quinine. TG, but not FFA are more elevated in control than in quinine. * p < 0.05, **p < 0.01, ***p < 0.001.
Figure 4
Figure 4
Body weight and fat mass of WT and Trpm5 knockout mice on control diet or diet + 0.1% quinine. The p values for the effects of diet, genotype and the interaction are shown below each graph. Body weight and fat mass gains are significantly diminished by quinine. Fat mass gain is significantly lower in Trpm5 KO mice. There is a trend for interaction diet*genotype for body weight, were the effect of quinine is larger in the WT than in the knockout background.
Figure 5
Figure 5
Faecal weight, and calorie, nitrogen and lipid contents of faeces from WT and Trpm5 KO mice consuming a regular diet or a 0.1% quinine supplemented diet. The p values for the effects of diet, genotype and the diet*genotype interaction are shown below each graph. FFA: free fatty acids, TG: triglycerides, CHL: cholesterol.
Figure 6
Figure 6
Body weight and body composition of obese wild type mice receiving control or 0.1% quinine supplemented high fat diet. Measures were taken at the beginning, 6 weeks and 11 weeks after the onset of the study. At 6 weeks after onset of the experiment, both lean and fat mass are lower in the quinine treated group, whereas at week 11 only lean mass is lower. * p < 0.05, **p < 0.01.
Figure 7
Figure 7
Activity and energy enpenditure. Twenty-four hour activity shown as mean events per 25 minute period, and energy expenditure of AIN-fed WT control, WT quinine and KO control mice show no difference between conditions. For energy expenditure, the dark period is represented by a grey box.
Figure 8
Figure 8
Inflamation markers. Plasma cytokine concentrations in individual WT mice fed a diet containing 0.1% quinine or a control diet showing elevated levels of cytokines in two control mice and one quinine fed mouse, but no difference in the levels of cytokines between diets.

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