title: Fisetin up-regulates the expression of adiponectin in 3T3-L1 adipocytes via the activation of silent mating type information regulation 2 homologue 1 (SIRT1)-deacetylase and peroxisome proliferator-activated receptors (PPARs).
abstract: Adiponectin, an adipokine, has been described as showing physiological benefits against obesity-related malfunctions and vascular dysfunction. Several natural compounds that promote the expression and secretion of adipokines in adipocytes could be useful for treating metabolic disorders. This study investigated the effect of fisetin, a dietary flavonoid, on the regulation of adiponectin in adipocytes using 3T3-L1 preadipocytes. The expression and secretion of adiponectin increased in 3T3-L1 cells upon treatment with fisetin in a dose-dependent manner. Fisetin-induced adiponectin secretion was inhibited by peroxisome proliferator-activated receptor (PPAR) antagonists. It was also revealed that fisetin increased the activities of PPARs and silent mating type information regulation 2 homologue 1 (SIRT1) in a dose-dependent manner. Furthermore, the up-regulation of adiponectin and the activation of PPARs induced by fisetin were prevented by a SIRT1 inhibitor. Fisetin also promoted deacetylation of PPAR γ coactivator 1 (PGC-1) and its interaction with PPARs. SIRT knockdown by siRNA significantly decreased both adiponectin production and PPARs-PGC-1 interaction. These results provide evidence that fisetin promotes the gene expression of adiponectin through the activation of SIRT1 and PPARs in adipocytes.
authors.affiliation: Department of Applied Bioscience, College of Life Science, CHA University , Gyeonggi-do 463-400, Republic of Korea.
authors.forename: Taewon
authors.initials: T
authors.lastname: Jin
authors.forename: Oh Yoen
authors.initials: OY
authors.lastname: Kim
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Shin
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Sung Sook
authors.initials: SS
authors.lastname: Lee
authors.forename: Ye Sun
authors.initials: YS
authors.lastname: Han
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Chung
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D051379:Mice; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics* / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D052242:Adiponectin; D005419:Flavonoids; D044948:Flavonols; D047492:Peroxisome Proliferator-Activated Receptors; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; C017875:fisetin
keywords: PPAR; SIRT1; adipocytes; adiponectin; fisetin