Genistein enhances expression of genes involved in fatty acid catabolism through activation of PPARalpha.
Although evidences are emerging that dietary isoflavones have beneficial effects in treatment of hyperlipidemia and cardiovascular diseases, the underlying molecular mechanism has not yet been extensively characterized. In this report, we showed that genistein, one of the major isoflavones, increased expression of genes involved in lipid catabolism such as carnitine palmitoyltransferase 1, liver form (CPT1L) in HepG2 cells, when assayed by real-time reverse-transcriptase polymerase chain reactions as well as Western blotting analysis. The increase in mRNA-level of CPT1L after genistein treatment was not changed in the presence of ICI182780, a potent inhibitor of estrogen receptor, suggesting that this effect of genistein was estrogen receptor-independent. Since these genes involved in fatty acid catabolism are considered putative downstream target genes of peroxisome proliferators-activated receptor alpha (PPARalpha), we examined whether expression of PPARalpha was modulated by genistein treatment. Interestingly, genistein induced expression of PPARalpha at both mRNA- and protein-level. Further, genistein activated transcriptional activity of PPARalpha, when determined by reporter gene analysis, suggesting genistein as a potential ligand for PPARalpha. Taken together, this study provides a picture of the regulatory action of genistein, as an activator of PPARalpha in fatty acid catabolism and potential use of genistein as lipid-lowering agent.
Kim
Sujong
S
Department of Biochemistry, College of Medicine, Hanyang University, Seoul 133-791, South Korea.
Shin
Hye-Jin
HJ
Kim
Sun Young
SY
Kim
Ji Hyun
JH
Lee
Yong Sung
YS
Kim
Duck-Hee
DH
Lee
Mi-Ock
MO
D045744:Cell Line, Tumor; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
D005227:Fatty Acids; D047493:PPAR alpha; D012333:RNA, Messenger; D019833:Genistein