Nobiletin suppresses adipocyte differentiation of 3T3-L1 cells by an insulin and IBMX mixture induction

Biochim Biophys Acta. 2012 Apr;1820(4):461-8. doi: 10.1016/j.bbagen.2011.11.015. Epub 2011 Dec 8.


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.

General significance: 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.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 3T3-L1 Cells
  • Adipocytes / cytology*
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Antioxidants / pharmacology
  • Cell Differentiation / drug effects
  • Cell Line
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Dexamethasone / pharmacology
  • Down-Regulation
  • Flavones / pharmacology*
  • Gene Expression / drug effects
  • Glucocorticoids / pharmacology
  • Insulin / pharmacology
  • Mice
  • Obesity / drug therapy
  • PPAR gamma / biosynthesis*
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphorylation
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction


  • Antioxidants
  • Cyclic AMP Response Element-Binding Protein
  • Flavones
  • Glucocorticoids
  • Insulin
  • PPAR gamma
  • Phosphodiesterase Inhibitors
  • STAT5 Transcription Factor
  • Dexamethasone
  • nobiletin
  • 1-Methyl-3-isobutylxanthine