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- Title
Positive regulation of hepatic carnitine palmitoyl transferase 1A (CPT1A) activities by soy isoflavones and L–carnitine.
- Authors
Eui Seok Shin; Si Young Cho; Eun Hee Lee; Sang Jun Lee; Ih Seop Chang; Tae Ryong Lee
- Abstract
Background Genistein increases CPT1A, a rate-limiting enzyme in the β-oxidation pathway, enzyme activity by increasing CPT1A transcription in HepG2 cells and, consequently, suppresses high fat induced obesity in C57BL/6J mice. Genistein and daidzein are the most abundant isoflavones in soy. Aim of study To investigate the effect of co-treatment of genistein and L-carnitine on CPT1A enzyme activity and to determine whether daidzein also increases CPT1A activity and to establish a cell line that can be used to screen chemicals to regulate CPT1A transcription. Methods The enzyme activities of CPT1A were determined after HepG2 cells were incubated with 10 µM genistein or 10 µM daidzein or 1 mM L-carnitine or in combination with 10 µM genistein and 1 mM L-carnitine or in combination with 10 µM daidzein and 1 mM L-carnitine. The mRNA expression levels of CPT1A were determined by real time PCR method after HepG2 cells were incubated with 10 µM genistein or 10 µM daidzein. A suggested CPT1A promoter region was cloned from human genomic DNA and the CPT1A promoter-luciferase reporter gene construct was made, and the promoter-reporter gene construct was transfected into human hepatoma cell line Huh7. Results The enzyme activity of CPT1A was at least 2.3-fold higher in L-carnitine and genistein co-treated HepG2 cells than either single-agent treated cells. Daidzein also significantly increased the mRNA expression of CPT1A as well as the enzyme activity of CPT1A. A stable Huh7 cell line,which was selected after Huh7 cells were transfected with CPT1A promoter luciferase reporter gene construct, was characterized by confirming that luciferase activity of the cell line can be regulated by genistein and daidzein as well as clofibrate, a well-known CPT1A mRNA up-regulating drug. Conclusions Genistein and daidzein can up-regulate CPT1A enzyme activity through up-regulation of CPT1A transcription. Co-treatment of L-carnitine and genistein additively increases CPT1A enzyme activity in HepG2 cells. A stable Huh7 cell line transfected with the CPT1A promoter luciferase reporter gene was established and characterized.
- Subjects
CARNITINE; ISOFLAVONES; ENZYMES; LABORATORY mice; CELL lines
- Publication
European Journal of Nutrition, 2006, Vol 45, Issue 3, p159
- ISSN
1436-6207
- Publication type
Article
- DOI
10.1007/s00394-005-0576-5