title: Nobiletin suppresses adipocyte differentiation of 3T3-L1 cells by an insulin and IBMX mixture induction.
abstract: BACKGROUND
  Nobiletin is a citrus flavonoid which possesses the flavone structure with six methoxy groups. Although nobiletin has been reported to display anti-inflammatory, anti-tumor, and anti-diabetes activities, its effect on adipocyte differentiation remained unclear. In the present study, we investigated the effect of nobiletin on the differentiation of 3T3-L1 preadipocytes into adipocytes.
  
  
  METHODS
  3T3-L1 preadipocytes were treated with nobiletin under various differentiation conditions. The effect of nobiletin on adipocyte differentiation was evaluated by oil red O staining, real-time RT-PCR, and Western blotting.
  
  
  RESULTS
  Nobiletin significantly suppressed the differentiation of 3T3-L1 preadipocytes into adipocytes, upon induction with insulin together with a cAMP elevator such as 3-isobutyl-1-methylxanthine (IBMX), by downregulating the expression of the gene encoding peroxisome proliferator-activated receptor (PPAR) γ2. In addition, nobiletin decreased the phosphorylation of cAMP-response element-binding protein (CREB) and strongly enhanced the phophorylation of signal transducer and activator of transcription (STAT) 5.
  
  
  CONCLUSIONS
  Nobiletin has a suppressive effect on the differentiation of preadipocytes into adipocytes when cells were induced with a general differentiation cocktail such as insulin, IBMX, and dexamethasone.
authors.affiliation: Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Kanda
authors.forename: Kosuke
authors.initials: K
authors.lastname: Nishi
authors.forename: Ayumu
authors.initials: A
authors.lastname: Kadota
authors.forename: Sogo
authors.initials: S
authors.lastname: Nishimoto
authors.forename: Ming-Cheh
authors.initials: MC
authors.lastname: Liu
authors.forename: Takuya
authors.initials: T
authors.lastname: Sugahara
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D047309:Flavones / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D047495:PPAR gamma / Q000096:biosynthesis*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D017362:Cyclic AMP Response Element-Binding Protein; D047309:Flavones; D005938:Glucocorticoids; D007328:Insulin; D047495:PPAR gamma; D010726:Phosphodiesterase Inhibitors; D050799:STAT5 Transcription Factor; D003907:Dexamethasone; C008661:nobiletin; D015056:1-Methyl-3-isobutylxanthine