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Ucp1 expression in brown adipose tissue (BAT) is induced by cold temperatures and is fully consistent with temperature adaptation and thermogenesis. Transcription of the Ucp1 gene is increased within minutes of cold exposure. Beige adipocytes are mainly in the subcutaneous white adipose tissues (WAT) and they arise postnatally in response to chronic cold exposure. This process is often referred as the browning of WAT. The aim of this study was to compare the cold induced metabolic and Ucp1 expression differences between WFS1-deficient mice and their wild-type littermates. Experiments were performed with 2–3 months old male and female F2 hybrids (129S6/SvEvTac × 129S6/SvEvTac). Five to twelve WFS1-deficient mice and wild-type mice were used in the study. Mice were kept at 8–12°C up to 7 days and metabolic effect was measured with calorimetric cages (TSE Phenomaster). Ucp1 expression was measured in BAT and WAT with qPCR (Applied Biosystems). The results of measurements showed that WFS1-deficient mice have significantly higher energy metabolism and higher Ucp1 expression in BAT and WAT after cold exposure. In conclusion, our results show that WFS1-deficient mice have a stronger response to cold exposure and upregulation of Ucp1 in BAT and WAT. Thus suggesting that WFS1-deficient mice have changes in regulation of thermogenesis that should be studied further.

Ucp1 expression in brown adipose tissue (BAT) is induced by cold temperatures and is fully consistent with temperature adaptation and thermogenesis. Transcription of the Ucp1 gene is increased within minutes of cold exposure. Beige adipocytes are mainly in the subcutaneous white adipose tissues (WAT) and they arise postnatally in response to chronic cold exposure. This process is often referred as the browning of WAT. The aim of this study was to compare the cold induced metabolic and Ucp1 expression differences between WFS1-deficient mice and their wild-type littermates. Experiments were performed with 2–3 months old male and female F2 hybrids (129S6/SvEvTac × 129S6/SvEvTac). Five to twelve WFS1-deficient mice and wild-type mice were used in the study. Mice were kept at 8–12°C up to 7 days and metabolic effect was measured with calorimetric cages (TSE Phenomaster). Ucp1 expression was measured in BAT and WAT with qPCR (Applied Biosystems). The results of measurements showed that WFS1-deficient mice have significantly higher energy metabolism and higher Ucp1 expression in BAT and WAT after cold exposure. In conclusion, our results show that WFS1-deficient mice have a stronger response to cold exposure and upregulation of Ucp1 in BAT and WAT. Thus suggesting that WFS1-deficient mice have changes in regulation of thermogenesis that should be studied further.

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.

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.

Wolfram syndrome, an autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and optic atrophy, is caused by mutations in the wolframin (Wfs1) gene. Wfs1 negatively regulates endoplasmic reticulum (ER) stress signalling and therefore have a role in the pathogenesis of diabetes and regulation of metabolism. One cardinal feature of Wfs1 mutant mice is their significantly reduced body weight. The real mechanism of weight loss is not known, but these mice develop normally until the age of 8 weeks. After this period weight loss starts. We recently found significant up-regulation of TRPM8 gene in the hippocampus of Wfs1 mutant mice. TRPM8 is menthol receptor and is involved in the regulation of energy metabolism. In present study we analysed metabolic activity and sensitivity of Wfs1 mutant mice to the menthol stimulation. We found that Wfs1 mutant mice have elevated metabolic activity in metabolic cages. Moreover, menthol induced significant increase in basal metabolic activity in Wfs1 mutant mice. Over-activation of TRPM8 receptor can explain increased metabolic rate in Wfs1 mutant mice and their reduced body weight.

Wolfram syndrome, an autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and optic atrophy, is caused by mutations in the wolframin (Wfs1) gene. Wfs1 negatively regulates endoplasmic reticulum (ER) stress signalling and therefore have a role in the pathogenesis of diabetes and regulation of metabolism. One cardinal feature of Wfs1 mutant mice is their significantly reduced body weight. The real mechanism of weight loss is not known, but these mice develop normally until the age of 8 weeks. After this period weight loss starts. We recently found significant up-regulation of TRPM8 gene in the hippocampus of Wfs1 mutant mice. TRPM8 is menthol receptor and is involved in the regulation of energy metabolism. In present study we analysed metabolic activity and sensitivity of Wfs1 mutant mice to the menthol stimulation. We found that Wfs1 mutant mice have elevated metabolic activity in metabolic cages. Moreover, menthol induced significant increase in basal metabolic activity in Wfs1 mutant mice. Over-activation of TRPM8 receptor can explain increased metabolic rate in Wfs1 mutant mice and their reduced body weight.

Wolfram syndrome, an autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and optic atrophy, is caused by mutations in the wolframin (WFS1) gene. WFS1 negatively regulates endoplasmic reticulum (ER) stress signalling and therefore have a role in the pathogenesis of diabetes. Valproic acid (VPA), a widely used anticonvulsant and mood-stabilizing drug, normalized the glucose intolerance in Wfs1 mutant mice, but had no effect on the course of glucose tolerance in wild-type (WT) mice. The aim of this study was to investigate insulin secretion in isolated pancreatic islets of WFS1-deficient (Wfs1KO) mice and also evaluate insulin secretion in the presence of VPA. In addition, the content of proinsulin in the isolated islets was measured. In general Wfs1KO pancreatic islets secreted less insulin compared to WT and Wfs1HZ islets. Differences in proinsulin amount were not statistically significant although there was a trend that Wfs1KO had an increased level of proinsulin. We found significantly reduced insulin secretion in Wfs1 mutants and no effect of VPA treatment. This study was supported by the Frontiers of Functional Genomics and by The European Regional Development Fund.

Wolfram syndrome, an autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and optic atrophy, is caused by mutations in the wolframin (WFS1) gene. WFS1 negatively regulates endoplasmic reticulum (ER) stress signalling and therefore have a role in the pathogenesis of diabetes. Valproic acid (VPA), a widely used anticonvulsant and mood-stabilizing drug, normalized the glucose intolerance in Wfs1 mutant mice, but had no effect on the course of glucose tolerance in wild-type (WT) mice. The aim of this study was to investigate insulin secretion in isolated pancreatic islets of WFS1-deficient (Wfs1KO) mice and also evaluate insulin secretion in the presence of VPA. In addition, the content of proinsulin in the isolated islets was measured. In general Wfs1KO pancreatic islets secreted less insulin compared to WT and Wfs1HZ islets. Differences in proinsulin amount were not statistically significant although there was a trend that Wfs1KO had an increased level of proinsulin. We found significantly reduced insulin secretion in Wfs1 mutants and no effect of VPA treatment. This study was supported by the Frontiers of Functional Genomics and by The European Regional Development Fund.