Sesamin ingestion regulates the transcription levels of hepatic metabolizing enzymes for alcohol and lipids in rats.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results suggested that sesamin ingestion regulated the transcription levels of hepatic metabolizing enzymes for alcohol and lipids.
Kiso
Yoshinobu
Y
Suntory Institute for Health Care Science, Osaka, Japan. Yoshinobu_Kiso@suntory.co.jp
Tsuruoka
Nobuo
N
Kidokoro
Ayako
A
Matsumoto
Ichiro
I
Abe
Keiko
K
D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000818:Animals; D004149:Dioxoles / Q000494:pharmacology*; D000431:Ethanol / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017705:Lignans / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020675:Peroxisomes / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
D004149:Dioxoles; D017705:Lignans; D000431:Ethanol; D000444:Aldehyde Dehydrogenase; C054125:sesamin