Correlation of suppressed linoleic acid metabolism with the hypocholesterolemic action of eritadenine in rats

The dose-dependent effects of dietary eritadenine on the metabolism of linoleic acid and on the plasma cholesterol concentration were investigated to clarify the mechanism of the hypocholesterolemic action of eritadenine in rats. Rats were fed control or eritadenine-supplemented (2 to 20 mg/kg) diets for 14 d. Eritadenine supplementation significantly decreased both the plasma cholesterol concentration and the 20∶4n−6/18∶2n−6 ratio of liver microsomal and plasma phosphatidylcholine (PC) in a dose-dependent manner. Eritadenine was also found to decrease the activity of Δ6 desaturase in liver microsomes; these was significant correlation between the Δ6-desaturase activity and the 20∶4n−6/18∶2n−6 ratio in the PC of liver microsomes (r=0.989, P<0.001) or plasma (r=0.986, P<0.001). Certain plasma PC molecular species, as represented by 16:0-18:2, were increased by eritadenine in a dose-dependent manner, and certain plasma PC molecular species, as represented by 18:0-20:4, were conversely decreased by eritadenine. There was a significant correlation between the plasma total cholesterol concentration and the proportion of the sum of plasma PC molecular species which contain 18:1 or 18:2 in the sn-2 position. These results support the idea that the suppression of linoleic acid metabolism by eritadenine might be associated with the hypocholesterolemic action of eritadenine.