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

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53 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 languageEnglish
Pages (from-to)698-708
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1831
Issue number4
DOIs
Publication statusPublished - 2013 Apr 1

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Keywords

  • Cyanidin
  • Hepatocyte
  • Lipid metabolism
  • PPAR

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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