Nobiletin Suppresses Adipogenesis by Regulating the Expression of Adipogenic Transcription Factors and the Activation of AMP-Activated Protein Kinase (AMPK)

The objective of this study was to elucidate the effect of nobiletin (5,6,7,8,3',4'-hexamethoxyflavone) on adipogenesis in 3T3-L1 cells. To determine the effect of nobiletin on adipogenesis, preadipocyte differentiation was induced in the presence or absence of nobiletin (10-100 mu M) for 4 days. The results revealed that nobiletin markedly inhibited lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity and blocked the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptors (PPAR gamma) and CCAAT/enhancer binding proteins (C/EBP alpha). Moreover, nobiletin significantly increased AMP-activated protein kinase (AMPK), a major regulator of cellular energy balance, phosphorylation, and intracellular reactive oxygen species (ROS) generation. This study also investigated the involvement of AMPK in the expression of a major transcription factor, PPAR gamma. It was found that pretreatment with compound C, a cell permeable inhibitor of AMPK, abolished the inhibitory effects of nobile tin on PPAR gamma expression. The results suggest that nobiletin exerts antiadipogenic effects through modulation of the PPAR gamma and AMPK signaling pathway and, therefore, may be a promising antiobesity agent.