Eritadenine, a hypocholesterolemic factor of Lentinus edodes mushroom, has a wide range of effects on lipid metabolism such as an increase in the liver microsomal phosphatidylethanolamine (PE) concentration, a decrease in the liver microsomal Δ6-desaturase activity, and an alteration of the fatty acid and molecular species profile of liver and plasma lipids. In this study, the time-dependent effects of dietary eritadenine on several variables concerning lipid metabolism were investigated in rats to clarify the sequence of metabolic changes caused by eritadenine, with special interest in the association of the liver microsomal phospholipid profile and the activity of Δ6-desaturase. The effect of dietary eritadenine on the abundance of mRNA for Δ6-desaturase was also investigated. When the time required for a half-change of variables was estimated during the first 5 days after the change from the control diet to the eritadenine-supplemented (50 mg/kg) diet, the change rates of the variables were fastest in the following order: alteration of the liver microsomal phospholipid profile>decrease in liver microsomal Δ6-desaturase activity>alteration of the fatty acid and molecular species profiles of microsomal and plasma phosphatidylcholine (PC)>decrease in the plasma cholesterol concentration. There was a significant correlation between the Δ6-desaturase activity and liver microsomal PE concentration, but not PC concentration, or the proportion of PC and PE or the PC/PE ratio. The suppression of Δ6-desaturase activity by dietary eritadenine was accompanied by a significant reduction in the abundance of mRNA for the enzyme. These results suggest that dietary eritadenine might suppress the activity of liver microsomal Δ6-desaturase by altering the microsomal phospholipid profile, as represented by an increase in PE concentration, and that the effect of eritadenine is mediated by the regulation of gene expression.

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