Effect of Diet Restriction on Renal Glutathione Metabolism in Mice

Various benefits for the maintenance of metabolic homeostasis can be obtained through dietary restriction. Short-term fasting of mice may induce systemic metabolic remodeling, which may have a significant effect on the level of endogenous metabolites. This study was conducted to examine metabolic changes of sulfur-containing substances in the kidneys of fasted mice over 48 h. No change in the concentration of renal methionine was observed over 48 h; however, significant decreases in the concentrations of S-adenosylmethionine and S-adenosylhomocysteine were observed at both 24 and 48 h after fasting. A significant decrease in the concentration of renal cysteine was observed from 24 h, and this was maintained at 48 h. A significant decrease in the concentration of glutathione (GSH) was observed in the kidney at 48 h, whereas increased concentrations of taurine were observed 48 h after fasting. Although significantly increased expression levels of BHMT were observed, markedly decreased expression levels of CβS were observed at 48 h after fasting, indicating activated generation of methionine, but downregulation of cysteine synthesis. The expression level of γ-GCL was not altered by fasting for 48 h; however, a significant increase of cysteine sulfinate decarboxylase mediating the taurine synthesis was observed. Significantly decreased protein expression levels of solute carrier family 7 member 11, which imports extracellular cystine, were observed at 48 h. These results suggest that the renal methionine concentration was maintained during short-term fasting through an increase in the re-methylation of homocysteine. Moreover, a reduction in the concentration of cysteine was the result of an increase in the synthesis of taurine and a decrease in the uptake of extracellular cystine, which may result in a decreased concentration of renal GSH.