Sesamin Ingestion Regulates the Transcription Levels of Hepatic Metabolizing Enzymes for Alcohol and Lipids in Rats

Abstract

Sesamin, a major lignan in sesame seeds, has multiple functions such as stimulation effect of ethanol metabolism in mice and human, and prevention of ethanol-induced fatty liver in rats. However, the mechanism has not been clarified yet. The changes of gene expression were investigated in rats given 250 mg/kg of sesamin (sesamin rats) or vehicle (control rats) for three days by using a DNA microarray analysis. At 4 hr after the final ingestion, the profiles of gene expression in rat livers were compared. The analysis showed that 38 transcripts were up-regulated with a significant change of more than two-fold and eight transcripts were down-regulated with a significant change to less than half in the livers of sesamin rats versus control rats. The gene expression levels of the early stage enzymes of beta-oxidation including long-chain acyl-CoA synthetase, very long-chain acyl-CoA synthetase and carnitine palmitoyltransferase were not changed, however, those of the late stage enzymes of beta-oxidation including trifunctional enzyme in mitochondria, and acyl-CoA oxidase, bifunctional enzyme and 3-ketoacyl-CoA thiolase in peroxisomes, were significantly increased by sesamin ingestion. Also, in sesamin rats, the gene expression of aldehyde dehydrogenase was increased about three-fold, whereas alcohol dehydrogenase, liver catalase and CYP2E1 were not changed. Changes in the gene expression of alcohol- and aldehyde-metabolizing enzymes observed in a DNA microarray were also confirmed by a real-time PCR method. These results suggested that sesamin ingestion regulated the transcription levels of hepatic metabolizing enzymes for alcohol and lipids.