Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-α

Ji Hae Lee; Hee jin Jun; Minh Hien Hoang; Yaoyao Jia; Xiang Hua Han; Dong Ho Lee; Hak Ju Lee; Bang Yeon Hwang; Sung Joon Lee

doi:10.1016/j.bbrc.2012.05.025

Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-α

Ji Hae Lee, Hee jin Jun, Minh Hien Hoang, Yaoyao Jia, Xiang Hua Han, Dong Ho Lee, Hak Ju Lee, Bang Yeon Hwang, Sung Joon Lee

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

9 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor-alpha (PPARα) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPARα agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPARα agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts. Results of time-resolved fluorescence resonance energy transfer analyses suggested that the compound interacted directly with the ligand-binding domain of PPARα. Cultured hepatocytes stimulated with catalposide exhibited significantly reduced cellular triglyceride concentrations, by 21%, while cellular uptake of fatty acids was increased, by 70% (. P<0.05). Quantitative PCR analysis revealed that the increase in cellular fatty acid uptake was due to upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells stimulated with catalposide. Additionally, expression of genes related to fatty acid oxidation and high-density lipoprotein metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed. In conclusion, catalposide is hypolipidemic by activation of PPARα via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.

Original language	English
Pages (from-to)	568-572
Number of pages	5
Journal	Biochemical and biophysical research communications
Volume	422
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2012.05.025
Publication status	Published - 2012 Jun 15

Bibliographical note

Funding Information:
This study was supported by the Korean Forest Service (Forest Science & Technology Project No. S120909L130110), the Technology Development Program for Fisheries of the Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea (iPET, F20926409H220000110), and the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (20100028180). The SPR instrument was provided by the Korea Basic Science Institute. We thank Hea-Won Kim for technical assistance.

Keywords

Catalposide
Hepatocyte
Lipid metabolism
Peroxisome proliferator receptor

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2012.05.025

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title = "Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-α",

abstract = "Peroxisome proliferator-activated receptor-alpha (PPARα) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPARα agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPARα agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts. Results of time-resolved fluorescence resonance energy transfer analyses suggested that the compound interacted directly with the ligand-binding domain of PPARα. Cultured hepatocytes stimulated with catalposide exhibited significantly reduced cellular triglyceride concentrations, by 21%, while cellular uptake of fatty acids was increased, by 70% (. P<0.05). Quantitative PCR analysis revealed that the increase in cellular fatty acid uptake was due to upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells stimulated with catalposide. Additionally, expression of genes related to fatty acid oxidation and high-density lipoprotein metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed. In conclusion, catalposide is hypolipidemic by activation of PPARα via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.",

keywords = "Catalposide, Hepatocyte, Lipid metabolism, Peroxisome proliferator receptor",

author = "Lee, {Ji Hae} and Jun, {Hee jin} and Hoang, {Minh Hien} and Yaoyao Jia and Han, {Xiang Hua} and Lee, {Dong Ho} and Lee, {Hak Ju} and Hwang, {Bang Yeon} and Lee, {Sung Joon}",

note = "Funding Information: This study was supported by the Korean Forest Service (Forest Science & Technology Project No. S120909L130110), the Technology Development Program for Fisheries of the Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea (iPET, F20926409H220000110), and the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (20100028180). The SPR instrument was provided by the Korea Basic Science Institute. We thank Hea-Won Kim for technical assistance.",

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T1 - Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-α

AU - Lee, Ji Hae

AU - Jun, Hee jin

AU - Hoang, Minh Hien

AU - Jia, Yaoyao

AU - Han, Xiang Hua

AU - Lee, Dong Ho

AU - Lee, Hak Ju

AU - Hwang, Bang Yeon

AU - Lee, Sung Joon

N1 - Funding Information: This study was supported by the Korean Forest Service (Forest Science & Technology Project No. S120909L130110), the Technology Development Program for Fisheries of the Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea (iPET, F20926409H220000110), and the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (20100028180). The SPR instrument was provided by the Korea Basic Science Institute. We thank Hea-Won Kim for technical assistance.

PY - 2012/6/15

Y1 - 2012/6/15

N2 - Peroxisome proliferator-activated receptor-alpha (PPARα) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPARα agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPARα agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts. Results of time-resolved fluorescence resonance energy transfer analyses suggested that the compound interacted directly with the ligand-binding domain of PPARα. Cultured hepatocytes stimulated with catalposide exhibited significantly reduced cellular triglyceride concentrations, by 21%, while cellular uptake of fatty acids was increased, by 70% (. P<0.05). Quantitative PCR analysis revealed that the increase in cellular fatty acid uptake was due to upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells stimulated with catalposide. Additionally, expression of genes related to fatty acid oxidation and high-density lipoprotein metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed. In conclusion, catalposide is hypolipidemic by activation of PPARα via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.

AB - Peroxisome proliferator-activated receptor-alpha (PPARα) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPARα agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPARα agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts. Results of time-resolved fluorescence resonance energy transfer analyses suggested that the compound interacted directly with the ligand-binding domain of PPARα. Cultured hepatocytes stimulated with catalposide exhibited significantly reduced cellular triglyceride concentrations, by 21%, while cellular uptake of fatty acids was increased, by 70% (. P<0.05). Quantitative PCR analysis revealed that the increase in cellular fatty acid uptake was due to upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells stimulated with catalposide. Additionally, expression of genes related to fatty acid oxidation and high-density lipoprotein metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed. In conclusion, catalposide is hypolipidemic by activation of PPARα via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.

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ER -

Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-α

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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