Abstract
To investigate the underlying mechanism of targets of cyanidin, a flavonoid, which exhibits potent anti-atherogenic activities in vitro and in vivo, a natural chemical library that identified potent agonistic activity between cyanidin and peroxisome proliferator-activated receptors (PPAR) was performed. Cyanidin induced transactivation activity in all three PPAR subtypes in a reporter gene assay and time-resolved fluorescence energy transfer analyses. Cyanidin also bound directly to all three subtypes, as assessed by surface plasmon resonance experiments, and showed the greatest affinity to PPARα. These effects were confirmed by measuring the expression of unique genes of each PPAR subtype. Cyanidin significantly reduced cellular lipid concentrations in lipid-loaded steatotic hepatocytes. In addition, transcriptome profiling in lipid-loaded primary hepatocytes revealed that the net effects of stimulation with cyanidin on lipid metabolic pathways were similar to those elicited by hypolipidemic drugs. Cyanidin likely acts as a physiological PPARα agonist and potentially for PPARβ/δ and γ, and reduces hepatic lipid concentrations by rewiring the expression of genes involved in lipid metabolic pathways.
Original language | English |
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Pages (from-to) | 698-708 |
Number of pages | 11 |
Journal | Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids |
Volume | 1831 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2013 Apr |
Bibliographical note
Funding Information:This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology ( 20100028180 ), the Korean Forest Service (Forest Science & Technology Project No. S120909L130110 ), the Cooperative Research Program for Agriculture Science & Technology Development (No. 201203013026150010400 ) Rural Development Administration, Republic of Korea . We thank Haewon Kim for technical assistance and to Prof Hyun-Gyu Song for the advice on FRET analysis. The SPR instrument was provided by the Korea Basic Science Institute.
Keywords
- Cyanidin
- Hepatocyte
- Lipid metabolism
- PPAR
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology