Cyanidin is an agonistic ligand for peroxisome proliferator-activated receptor-alpha reducing hepatic lipid

Yaoyao Jia; Jin Young Kim; Hee Jin Jun; Sun Joong Kim; Ji Hae Lee; Minh Hien Hoang; Hyun Sook Kim; Hyo Ihl Chang; Kwang Yeon Hwang; Soo Jong Um; Sung Joon Lee

doi:10.1016/j.bbalip.2012.11.012

Cyanidin is an agonistic ligand for peroxisome proliferator-activated receptor-alpha reducing hepatic lipid

Yaoyao Jia, Jin Young Kim, Hee Jin Jun, Sun Joong Kim, Ji Hae Lee, Minh Hien Hoang, Hyun Sook Kim, Hyo Ihl Chang, Kwang Yeon Hwang, Soo Jong Um, Sung Joon Lee

Research output: Contribution to journal › Article › peer-review

78 Citations (Scopus)

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	https://doi.org/10.1016/j.bbalip.2012.11.012
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

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10.1016/j.bbalip.2012.11.012

Cite this

Jia, Y., Kim, J. Y., Jun, H. J., Kim, S. J., Lee, J. H., Hoang, M. H., Kim, H. S., Chang, H. I., Hwang, K. Y., Um, S. J., & Lee, S. J. (2013). Cyanidin is an agonistic ligand for peroxisome proliferator-activated receptor-alpha reducing hepatic lipid. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1831(4), 698-708. https://doi.org/10.1016/j.bbalip.2012.11.012

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title = "Cyanidin is an agonistic ligand for peroxisome proliferator-activated receptor-alpha reducing hepatic lipid",

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.",

keywords = "Cyanidin, Hepatocyte, Lipid metabolism, PPAR",

author = "Yaoyao Jia and Kim, {Jin Young} and Jun, {Hee Jin} and Kim, {Sun Joong} and Lee, {Ji Hae} and Hoang, {Minh Hien} and Kim, {Hyun Sook} and Chang, {Hyo Ihl} and Hwang, {Kwang Yeon} and Um, {Soo Jong} and Lee, {Sung Joon}",

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. ",

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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

N1 - 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.

PY - 2013/4

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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.

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ER -

Cyanidin is an agonistic ligand for peroxisome proliferator-activated receptor-alpha reducing hepatic lipid

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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