Chronic Exercise and Genetic Background Affect Glucose Homeostasis in Mice

Objectives: This study compared parameters related to glucose homeostasis and the proteome of liver in mice susceptible (A/J) or resistant (129P3/J) to dental fluorosis in response to exposure to fluoride (F), with and without physical exercise.
Methods: A/J (S) and 129P3/J (R) male mice were divided into 3 groups (n=15/group/strain), according with the treatments received for 56 days: a) deionized drinking water and no exercise(I); b) drinking water containing 50ppmF (as NaF) and no exercise(II); c) drinking water containing 50ppmF and exercise (daily runs on a treadmill 5 days week for 60 minutes at high intensity; III). Plasma F, glucose and insulin were analyzed with the electrode, glucose-oxidase method or ELISA, respectively. Quantitative label-free proteomic analysis was conducted in the liver (n-LC-MS/MS and ProteinLynx Global Server software). Data were analyzed by 2-way ANOVA and Bonferronis tests (p<0.05).
Results: Plasma F concentrations were significantly higher in R mice, compared to S, but only for groups II and III, which had plasma F levels significantly higher than group I. The S mice, regardless the treatment, had higher plasma glucose levels than the R ones (significant for group II), while plasma insulin levels were similar. When the liver proteome of the S and R strains was compared, in groups I and II, there was an increase in proteins involved in energy flux and antioxidant enzymes in the S mice. In group III, there was a reduction in proteins involved in protein synthesis, energy metabolism and detoxification, but antioxidant enzymes were still increased in the S mice.
Conclusions: These results suggest an increased state of oxidative stress in S mice that is inherent to this strain and might be exacerbated upon treatment with F. In addition, S mice might benefit more of the effect of physical exercise on glucose homeostasis, upon exposure to F.