Soft drinks and monogenetic diabetes: a study on the Wolfram syndrome 1 (Wfs1) deficient mouse model

Abstract

Abbreviations: ANOVA -analysis of variance; ER -endoplasmic reticulum; HZ -heterozygous;KO -knock-out; WFS1 -Wolfram syndrome 1; WFS1 -Wolfram syndrome 1 gene in humans;Wfs1 -Wolfram syndrome 1 gene in mice; WT -wild-type. 2 AbstractIn a modern society, the risk of developing type II diabetes and obesity may be linked to the increased consumption of carbohydrate-rich drinks. Several genes, including Wolfram Syndrome 1 (WFS1), have been reported to increase susceptibility for developing type II diabetes. In this study we aimed to investigate the effect of chronic consumption of carbohydrate-rich drinks on weight gain, overall consumption of liquids, glucose tolerance and liver metabolism in Wfs1deficient mice. Wfs1-deficient and wild-type mice were divided into three groups that consumed regular Coca-Cola, 20% sucrose solution or water ad libitum as the only source of liquid. During the experiment, daily liquid consumption was determined. After 30 days, total weight gain of mice was calculated and glucose tolerance test was performed. The liver tissue was analysed by means of untargeted and targeted metabolomics using liquid chromatography-mass spectrometry.Weight gain was strongly affected by mouse genotype (p<0.001), their drink (p<0.001) and the interaction of both genotype and drink (p<0.001). Coca-Cola significantly increased liquid consumption in knock-out mice. There was an effect of the drink (p<0.001) and the interaction between the genotype and treatment (p=0.02) on blood glucose level while Coca-Cola and 20% sucrose solution exacerbated glucose intolerance in the knock-out mice. In untargeted metabolic profiling, the water consuming wild-type and heterozygous mice were found to be the most distinctive from the mice with all other genotype and drink combinations. Targeted analysis revealed interactions between the genotype and drink regarding to glycolysis and lipogenesis. In the wild-type animals, carbohydrate overload was alleviated by converting glucose to lipids. However, the same mechanism is not implemented in knock-out animals, as lipolysis and gluconeogenesis are upregulated by Wfs1 deficiency. In conclusion, our study demonstrates a 3 significant interaction between the genotype and the drink when comparing wild-type and Wfs1 knock-out mice consuming soft drinks.