title: Nobiletin suppresses adipogenesis by regulating the expression of adipogenic transcription factors and the activation of AMP-activated protein kinase (AMPK).
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.
authors.affiliation: Department of Food Science and Technology, College of Agriculture, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Youngmin
authors.initials: Y
authors.lastname: Choi
authors.forename: Younghwa
authors.initials: Y
authors.lastname: Kim
authors.forename: Hyeonmi
authors.initials: H
authors.lastname: Ham
authors.forename: Yooheon
authors.initials: Y
authors.lastname: Park
authors.forename: Heon-Sang
authors.initials: HS
authors.lastname: Jeong
authors.forename: Junsoo
authors.initials: J
authors.lastname: Lee
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D019440:Anti-Obesity Agents; D000975:Antioxidants; D004789:Enzyme Activation / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D047495:PPAR gamma / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D019440:Anti-Obesity Agents; D000975:Antioxidants; D047309:Flavones; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C008661:nobiletin; D055372:AMP-Activated Protein Kinases