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.
authors.affiliation: Department of Biotechnology, the Graduate School of Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Jun
authors.forename: Sun-Joong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ji-Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Minh Hien
authors.initials: MH
authors.lastname: Hoang
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Hyo Ihl
authors.initials: HI
authors.lastname: Chang
authors.forename: Kwang-Yeon
authors.initials: KY
authors.lastname: Hwang
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Um
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists; D048068:PPAR-beta / Q000819:agonists
chemical_list: D000872:Anthocyanins; D047493:PPAR alpha; D047495:PPAR gamma; D048068:PPAR-beta; C017154:cyanidin