Metabolic effects of menthol on WFS1-deficient mice

Previous experiments of RNA sequencing showed that Trpm8 gene was upregulated in the hippocampus of WFS1-deficient mice compared to wild-type littermates. TRPM8 is activated by cold (8–28°C) and chemicals, e.g. menthol, which induce cold sensation. TRP ion channels are used as primary transducers of thermal stimuli for thermosensation. The aim of this study was to compare the metabolic differences and dose-response effects to menthol between WFS1-deficient mice and their wild-type littermates. Experiments were performed with 9–12 months old male F2 hybrids (129S6/SvEvTac x 129S6/SvEvTac). Five to twelve WFS1-deficient mice and wild-type mice were used in the study. Different menthol doses were administrated by oral gavage and metabolic effect was measured with metabolic cages (TSE Phenomaster). The life span of WFS1-deficient and wild-type mice was investigated. The results of measurements showed that WFS1-deficient mice have significantly higher energy metabolism and shorter life span compared to WT mice and specific menthol doses had a significantly higher reaction on the energy metabolism of WFS1-deficient mice compared to WT mice. In conclusion, our results show that the shorter life span, metabolic changes and upregulation of Trpm8 gene in WFS1-deficient mice suggest that WFS1-deficient mice have serious metabolic dysfunctions. Menthol has an opposite effect on the WFS1-deficient mice metabolic parameters by increasing them compared to wild-type mice.