Nobiletin suppresses adipogenesis by regulating the expression of adipogenic transcription factors and the activation of AMP-activated protein kinase (AMPK)

Youngmin Choi, Younghwa Kim, Hyeonmi Ham, Yooheon Park, Heon Sang Jeong, Junsoo Lee

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

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 μM) 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 (PPARγ) and CCAAT/enhancer binding proteins (C/EBPα). 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, PPARγ. It was found that pretreatment with compound C, a cell permeable inhibitor of AMPK, abolished the inhibitory effects of nobiletin on PPARγ expression. The results suggest that nobiletin exerts antiadipogenic effects through modulation of the PPARγ and AMPK signaling pathway and, therefore, may be a promising antiobesity agent.

Original languageEnglish
Pages (from-to)12843-12849
Number of pages7
JournalJournal of Agricultural and Food Chemistry
Volume59
Issue number24
DOIs
StatePublished - 28 Dec 2011

Keywords

  • 3T3-L1
  • AMPK
  • intracellular ROS
  • Nobiletin
  • PPARγ

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