Abstract
In this study, we investigated the physiological regulation of energy metabolism in wild-type (WT) and WFS1-deficient (Wfs1KO) mice by measuring the effects of menthol treatment on the O2 consumption, CO2 production, rectal body temperature, and heat production. The basal metabolism and behavior was different between these genotypes as well as TRP family gene expressions. Wfs1KO mice had a shorter life span and weighed less than WT mice. The food and water intake of Wfs1KO mice was lower as well as the body temperature when compared to their WT littermates. Furthermore, Wfs1KO mice had higher basal O2 consumption, and CO2 and heat production than WT mice. In addition, Wfs1KO mice showed a higher response to menthol administration in comparison to WT mice. The strongest menthol effect was seen on different physiological measures 12 h after oral administration. The highest metabolic response of Wfs1KO mice was seen at the menthol dose of 10mg/kg. Menthol increased O2 consumption, and CO2 and heat production in Wfs1KO mice when compared to their WT littermates. In addition, the expression of Trpm8 gene was increased. In conclusion, our results show that the Wfs1KO mice develop a metabolic phenotype characterized with several physiological dysfunctions.
Highlights
The first description of Wolfram syndrome (WS), an autosomal recessive disorder, was reported in 1938
Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society
The experiments revealed that the dose of 10 mg/kg of a Transient receptor potential melastatin 8 (TRPM8) agonist, menthol, is most effective by increasing the heat production, O2 consumption, and CO2 production of Wfs1KO mice compared to WT mice
Summary
The first description of Wolfram syndrome (WS), an autosomal recessive disorder, was reported in 1938. The acronym DIDMOAD summarizes the most frequent findings: diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. The minimal criteria for diagnosis are diabetes mellitus and optic atrophy (Strom et al 1998). The cause of WS is the loss-of-function mutations in wolframin (Wfs1) gene (Strom et al 1998). Wfs is linked to the short arm of chromosome 4 p16.1 (Polymeropoulos et al 1994; Collier et al 1996). The Wfs gene encodes wolfamin (WFS1), a protein with 890 amino acid residues and a molecular mass of 100 kDa. WFS1 is a hydrophobic glycoprotein which contains nine transmembrane segments, with the N-terminus localized in the cytoplasma and the C-terminus in the endoplasmic reticulum lumen (Hofmann et al 2003)
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