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Hypocholesterolemic Action of Eritadenine Is Mediated by a Modification of Hepatic Phospholipid Metabolism in Rats¹

Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, Shizuoka 422, Japan

The hypocholesterolemic action of eritadenine, a compound found in the mushroom Lentinus edodes, was investigated in relation to its influence on phospholipid metabolism in the liver of rats fed diets containing different amounts of choline chloride (0, 2 and 8 g/kg diet). The time-dependent effect of eritadenine supplementation was also investigated. Eritadenine supplementation (50 mg/kg diet) significantly decreased the phosphatidylcholine (PC):phosphatidylethanolamine (PE) ratio in liver microsomes and the S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) ratio in the liver, in addition to the plasma cholesterol concentration, irrespective of dietary choline levels. There was a significant correlation between the plasma cholesterol concentration and the liver microsomal PC:PE ratio. Although eritadenine caused fatty liver when added to the diets containing 0 or 2 g/kg choline chloride, a high level (8 g/kg) of choline chloride fully prevented the eritadenine-induced fatty liver without diminution of hypocholesterolemic action. Both the PC:PE ratio and the SAM:SAH ratio decreased significantly prior to the decrease in the plasma cholesterol concentration (1 d vs. 2 d after) in response to eritadenine supplementation, supporting the hypothesis that the alteration of hepatic phospholipid metabolism may be a cause of the hypocholesterolemic action of eritadenine. These observations suggest that the essential hypocholesterolemic action of eritadenine might be associated with a modification of hepatic phospholipid metabolism rather than with the PC deficiency, due to the inhibition of PE N-methylation.

KEY WORDS: • eritadenine • choline • rats • cholesterol • phospholipids

¹ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

² To whom correspondence should be addressed.

Manuscript received 16 September 1994. Revision accepted 26 January 1995.