title: Scutellarin from Scutellaria baicalensis suppresses adipogenesis by upregulating PPARα in 3T3-L1 cells.
abstract: Adipocyte dysfunction is a major cause of obesity, which is associated strongly with many disorders including psychological and medical morbidities, metabolic abnormalities, and cardiovascular diseases as well as a series of cancers. This study investigated the antiadipogenic activity of scutellarin (1) in 3T3-L1 preadipocytes as well as the underlying molecular mechanisms. It was observed that 1 reduced adipocyte differentiation of 3T3-L1 cells potently, as evidenced by a decrease in cellular lipid accumulation. At the molecular level, mRNA expression of the master adipogenic transcription factors, PPARγ and C/EBPα, was decreased markedly. However, mRNA levels of C/EBPβ, the upstream regulator of PPARγ and C/EBPα, were not decreased by 1. Moreover, a dose-dependent upregulation of PPARα was observed for 1. Computational modeling indicated that 1 can bind to PPARα, γ, and δ each in a distinct manner, while it can activate PPARα only by forming a hydrogen bond with Y464, thus stabilizing the AF-2 helix and activating PPARα. Therefore, these results suggest that 1, a major component of Scutellaria baicalensis, attenuates fat cell differentiation by upregulating PPARα as well as downregulating the expression of PPARγ and C/EBPα, thus showing therapeutic potential for obesity-related diseases.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
authors.forename: Kaihui
authors.initials: K
authors.lastname: Lu
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Han
authors.forename: Hui Lin
authors.initials: HL
authors.lastname: Ting
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Liu
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D047310:Apigenin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005965:Glucuronates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D031364:Scutellaria baicalensis / Q000737:chemistry*; D012689:Sequence Homology, Nucleic Acid
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D005965:Glucuronates; D047493:PPAR alpha; D047495:PPAR gamma; C484876:scutellarin; D047310:Apigenin