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, Dongho Lee, Hak Ju Lee, Bang Yeon Hwang, Sung-Joon Lee

Research output: Contribution to journalArticle

7 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 languageEnglish
Pages (from-to)568-572
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume422
Issue number4
DOIs
Publication statusPublished - 2012 Jun 15

Fingerprint

PPAR alpha
Peroxisome Proliferator-Activated Receptors
Fatty Acids
Genes
Ligands
Hepatocytes
Seaweed
Gene Expression
Oxidation
Fluorescence Resonance Energy Transfer
Hypertriglyceridemia
Plant Extracts
HDL Lipoproteins
Cytoplasmic and Nuclear Receptors
Reporter Genes
Lipid Metabolism
Metabolism
Assays
Screening
Triglycerides

Keywords

  • Catalposide
  • Hepatocyte
  • Lipid metabolism
  • Peroxisome proliferator receptor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-α. / Lee, Ji Hae; Jun, Hee jin; Hoang, Minh Hien; Jia, Yaoyao; Han, Xiang Hua; Lee, Dongho; Lee, Hak Ju; Hwang, Bang Yeon; Lee, Sung-Joon.

In: Biochemical and Biophysical Research Communications, Vol. 422, No. 4, 15.06.2012, p. 568-572.

Research output: Contribution to journalArticle

Lee, Ji Hae ; Jun, Hee jin ; Hoang, Minh Hien ; Jia, Yaoyao ; Han, Xiang Hua ; Lee, Dongho ; Lee, Hak Ju ; Hwang, Bang Yeon ; Lee, Sung-Joon. / Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-α. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 422, No. 4. pp. 568-572.
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