Quinine controls body weight gain without affecting food intake in male C57BL6 mice

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.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.Quinine is a natural molecule extracted from the bark of the cinchona tree commonly used as a flavoring agent in tonic water and bitter lemon and, at higher doses, for the treatment of some forms of malaria. Consumption of quinine by rats strongly reduces food intake and body weight [1-7]. The decrease in food intake was initially attributed to the intense bitter taste of quinine but it was later shown that diminished food intake is observed with rats consuming a diet supplemented with quinine, but not with a diet supplemented with iso-bitter sucrose octaacetate, suggesting that palatability is not the only cause of decreased food intake in rats consuming quinine in the diet [1]. Furthermore it is unclear from the rat experiments whether there is a direct effect of quinine on body weight, independently of food intake. Quinine was recently shown to inhibit the activity of Trpm5 [8] a calcium activated cation channel expressed in the taste buds [9], gastrointestinal tract [10], pancreas [11] and other