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

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• 作者：Ji Hae Lee^a ; ^b ; ¹ ; Hee-jin Jun^a ; ^b ; ¹ ; Minh-Hien Hoang^a ; ^b ; Yaoyao Jia^a ; ^b ; Xiang Hua Han^d ; Dong-Ho Lee^b ; Hak-Ju Lee^c ; Bang Yeon Hwang^d ; ^{byhwang@chungbuk.ac.kr} ; Sung-Joon Lee^a ; ^b ; ^{junelee@korea.ac.kr}
• 关键词：Peroxisome proliferator receptor ; Catalposide ; Hepatocyte ; Lipid metabolism
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：15 June, 2012
• 卷：422
• 期：4
• 页码：568-572
• 文件大小：492 K

摘要

Peroxisome proliferator-activated receptor-alpha (PPAR伪) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPAR伪 agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPAR伪 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 PPAR伪. 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 PPAR伪 via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.