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 |
|---|---|
| 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 1 |
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Keywords
- Cyanidin
- Hepatocyte
- Lipid metabolism
- PPAR
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
Cyanidin is an agonistic ligand for peroxisome proliferator-activated receptor-alpha reducing hepatic lipid. / Jia, Yaoyao; Kim, Jin Young; Jun, Hee Jin; Kim, Sun Joong; Lee, Ji Hae; Hoang, Minh Hien; Kim, Hyun Sook; Chang, Hyo-Ihl; Hwang, Kwang Yeon; Um, Soo Jong; Lee, Sung-Joon.
In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1831, No. 4, 01.04.2013, p. 698-708.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cyanidin is an agonistic ligand for peroxisome proliferator-activated receptor-alpha reducing hepatic lipid
AU - Jia, Yaoyao
AU - Kim, Jin Young
AU - Jun, Hee Jin
AU - Kim, Sun Joong
AU - Lee, Ji Hae
AU - Hoang, Minh Hien
AU - Kim, Hyun Sook
AU - Chang, Hyo-Ihl
AU - Hwang, Kwang Yeon
AU - Um, Soo Jong
AU - Lee, Sung-Joon
PY - 2013/4/1
Y1 - 2013/4/1
N2 - 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.
AB - 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.
KW - Cyanidin
KW - Hepatocyte
KW - Lipid metabolism
KW - PPAR
UR - http://www.scopus.com/inward/record.url?scp=84873451171&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873451171&partnerID=8YFLogxK
U2 - 10.1016/j.bbalip.2012.11.012
DO - 10.1016/j.bbalip.2012.11.012
M3 - Article
C2 - 23228689
AN - SCOPUS:84873451171
VL - 1831
SP - 698
EP - 708
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
SN - 1388-1981
IS - 4
ER -