title: Suppression of Adipogenesis by 5-Hydroxy-3,6,7,8,3',4'-Hexamethoxyflavone from Orange Peel in 3T3-L1 Cells.
abstract: We reported previously that hydroxylated polymethoxyflavones (HPMFs) effectively suppressed obesity in high-fat-induced mouse. In this study, we further investigated the molecular mechanism of action of 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5-OH-HxMF), one of major HPMFs in orange peel. Treatment of 5-OH-HxMF effectively inhibited lipid accumulation by 55-60% in a dose-dependent manner. The 5-OH-HxMF attenuated adipogenesis through downregulating adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs), as well as downstream target fatty acid synthase and acetyl-CoA carboxylase (ACC). 5-OH-HxMF activated adenosine monophosphate-activated protein kinase signaling and silent mating type information regulation 1 (SIRTUIN 1 or SIRT1) in 3T3-L1 adipocytes to decrease lipid accumulation. In addition, the inhibition rate of lipid accumulation was compared between 5-OH-HxMF and 3,5,6,7,8,3',4'-heptamethoxyflavone (HpMF). 5-OH-HxMF inhibited lipid accumulation 15-20% more than HpMF did, indicating that hydroxyl group at position 5 can be a key factor in the suppression of adipogenesis.
authors.affiliation: 1 Department of Food Science and Human Nutrition, Citrus Research and Education Center, University of Florida , Lake Alfred, Florida, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2 Institute of Food Science and Technology, National Taiwan University , Taipei, Taiwan .
authors.forename: Pei-Sheng
authors.initials: PS
authors.lastname: Lee
authors.affiliation: 2 Institute of Food Science and Technology, National Taiwan University , Taipei, Taiwan .
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Chen
authors.affiliation: 3 Department of Food Science, Rutgers University , New Brunswick, New Jersey, USA.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.affiliation: 2 Institute of Food Science and Technology, National Taiwan University , Taipei, Taiwan .|4 Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, College of Life Science, Huanggang Normal University , Hubei, China .|5 Department of Medical Research, China Medical University Hospital, China Medical University , Taichung, Taiwan .|6 Department of Health and Nutrition Biotechnology, Asia University , Taichung, Taiwan .
authors.forename: Min-Hsiung
authors.initials: MH
authors.lastname: Pan
mesh_terms: D041721:3T3-L1 Cells; D000103:Acetyl-CoA Carboxylase; D000249:Adenosine Monophosphate / Q000378:metabolism; D017667:Adipocytes; D050156:Adipogenesis / Q000187:drug effects*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002957:Citrus / Q000737:chemistry*; D047309:Flavones / Q000494:pharmacology* / Q000627:therapeutic use; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use; D005638:Fruit / Q000737:chemistry; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D022763:CCAAT-Enhancer-Binding Protein-alpha; D047309:Flavones; D005419:Flavonoids; D047495:PPAR gamma; D010936:Plant Extracts; C521815:5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone; C059294:3,3',4',5,6,7,8-heptamethoxyflavone; D000249:Adenosine Monophosphate; D011494:Protein Kinases; D056564:Sirtuin 1; D000103:Acetyl-CoA Carboxylase
keywords: 3T3-L1; 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone; adipogenesis; medicinal food; orange peel