6-gingerol prevents adipogenesis and the accumulation of cytoplasmic lipid droplets in 3T3-L1 cells.
6-Gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) is one of the pungent constituents of Zingiber zerumbet (L) Smith (Zingiberaceae family). In this study, we investigated the effects of 6-gingerol on the inhibition of adipogenesis in 3T3-L1 cells. After treatment with 6-gingerol in differentiation medium for 4 or 8 days, the 3T3-L1 cells were lysed for experimental analysis. Cells were stained with Oil-Red-O to detect oil droplets in adipocytes. The 3T3-L1 cells were lysed and measured for triglyceride contents. The protein expression of adipogenesis-related transcription factor was evaluated by Western blot analysis. 6-Gingerol suppressed oil droplet accumulation and reduced the droplet size in a concentration (5-15 μg/ml)- and time-dependent manner. Treatment of 3T3-L1 cells with 6-gingerol reduced the protein levels of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α. Additionally, the protein levels of fatty acid synthase (FAS) and adipocyte-specific fatty acid binding protein (aP2) decreased upon treatment with 6-gingerol. Meanwhile, 6-gingerol diminished the insulin-stimulated serine phosphorylation of Akt (Ser473) and GSK3β (Ser9). These results suggest that 6-gingerol effectively suppresses adipogenesis and that it exerts its role mainly through the significant down-regulation of PPARγ and C/EBPα and subsequently inhibits FAS and aP2 expression. 6-Gingerol also inhibited differentiation in 3T3-L1 cells by attenuating the Akt/GSK3β pathway. Our findings provide important insights into the mechanisms underlying the anti-adipogenic activity of 6-gingerol.
Department of Internal Medicine, Pao Chien Hospital, Ping Tung City, Pingtung County, Taiwan, ROC.
Thing-Fong
TF
Tzeng
I-Min
IM
Liu
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology* / Q000627:therapeutic use; D003593:Cytoplasm / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005233:Fatty Alcohols / Q000494:pharmacology* / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D030521:Zingiberaceae / Q000737:chemistry*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D002396:Catechols; D050556:Fatty Acid-Binding Proteins; D005233:Fatty Alcohols; D000960:Hypolipidemic Agents; D007328:Insulin; D047495:PPAR gamma; D010936:Plant Extracts; C007845:gingerol; D064429:Fatty Acid Synthases