title: Flavonoid derivative (Fla-CN) inhibited adipocyte differentiation via activating AMPK and up-regulating microRNA-27 in 3T3-L1 cells.
abstract: Fla-CN (3-O-[(E)-4-(4-cyanophenyl)-2-oxobut-3-en-1-yl] kaempferol) is a semi-synthesized flavonoid derivative of tiliroside which exhibited anti-diabetic effect in vivo. Our previous study revealed the role of Fla-CN in anti-obesity and anti-diabetes in vivo, but the underlying mechanism remained to be addressed. The present study aimed to investigate the mechanism of anti-adipogenesis in vitro. Fla-CN markedly inhibited intracellular lipid accumulation in a dose-dependent manner, and the inhibitory effect was mainly limited to the early stage of adipocyte differentiation in vitro. Further investigations revealed that Fla-CN up-regulated the expression level of miR-27a/b and suppressed its target genes expression including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). Furthermore, the phosphorylation of AMP-activated protein kinase (AMPK) was also enhanced by Fla-CN in pre-adipocyte differentiation. These effects were abolished when cells were treated with miR-27a/b inhibitor and AMPK inhibitor Compound C. Additionally, Fla-CN reduced the expressions of adipocyte-specific genes such as sterol regulatory element-binding transcription factor 1c (SREBP-1c), fatty acid synthase (FAS) and adipocyte fatty acid binding protein (aP2). In conclusion, these results suggested a mechanism of Fla-CN for adipocyte differentiation inhibition of 3T3-L1 cells through miR-27a/b induction and AMPK activation.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, People's Republic of China.
authors.forename: Chun-Chun
authors.initials: CC
authors.lastname: Gan
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, People's Republic of China.
authors.forename: Tian-Wen
authors.initials: TW
authors.lastname: Ni
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, People's Republic of China; Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Qin
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, People's Republic of China. Electronic address: jinmeina@tmu.edu.cn.
authors.forename: Mei-Na
authors.initials: MN
authors.lastname: Jin
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, People's Republic of China; Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, People's Republic of China. Electronic address: duanhq@tmu.edu.cn.
authors.forename: Hong-Quan
authors.initials: HQ
authors.lastname: Duan
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D044949:Kaempferols / Q000494:pharmacology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C000611534:3-O-(4-(4-cyanophenyl)-2-oxobut-3-en-1-yl)kaempferol; D044949:Kaempferols; D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; D014157:Transcription Factors; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Adipocyte differentiation; Anti-obesity; Fla-CN; MicroRNA-27a/b