title: 5-Demethylnobiletin and 5-Acetoxy-6,7,8,3',4'-pentamethoxyflavone Suppress Lipid Accumulation by Activating the LKB1-AMPK Pathway in 3T3-L1 Preadipocytes and High Fat Diet-Fed C57BL/6 Mice.
abstract: Polymethoxyflavones (PMFs) and hydroxylated polymethoxyflavones (HPMFs), such as nobiletin (Nob) and 5-demethylnobiletin (5-OH-Nob), are unique flavonoids that are found exclusively in citrus peels. Nobiletin has been shown to suppress adipogenesis in vitro, but the antiadipogenic activity of 5-OH-Nob has not been investigated. Both nobiletin and 5-OH-Nob have poor aqueous solubility and low oral bioavailability. We employed chemical modification to produce the acetyl derivative of 5-OH-Nob, that is, 5-acetyloxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), to improve its bioavailability and bioactive efficiency. We found that 5-Ac-Nob reduced triacylglycerol (TG) content to a greater extent than 5-OH-Nob in 3T3-L1 preadipocytes. Orally administered 5-Ac-Nob resulted in a significant reduction in body weight, intra-abdominal fat, plasma and liver TG levels, and plasma cholesterol level in high fat diet-induced obese male C57BL/6J mice. The 5-Ac-Nob treatment decreased lipid accumulation by triggering the adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway to alter transcriptional factors or lipogenesis-related enzymes in vivo and in vitro.
authors.affiliation: Department of Food Science, Rutgers University , New Brunswick, New Jersey 08901, United States.|Institute of Food Sciences and Technology, National Taiwan University , Taipei 106, Taiwan.
authors.forename: Yen-Chen
authors.initials: YC
authors.lastname: Tung
authors.affiliation: Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization and Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains, Huanggang Normal University , Huanggang, Hubei China.
authors.forename: Shiming
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Food Science, Rutgers University , New Brunswick, New Jersey 08901, United States.
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Food Science, Rutgers University , New Brunswick, New Jersey 08901, United States.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Hung
authors.affiliation: Department of Food Science, Rutgers University , New Brunswick, New Jersey 08901, United States.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.affiliation: Department of Nutrition and Health Sciences, Kainan University , Taoyuan 33857, Taiwan.
authors.forename: Guor-Jien
authors.initials: GJ
authors.lastname: Wei
authors.affiliation: Institute of Food Sciences and Technology, National Taiwan University , Taipei 106, Taiwan.|Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization and Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains, Huanggang Normal University , Huanggang, Hubei China.|Department of Medical Research, China Medical University Hospital, China Medical University , Taichung, Taiwan.|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; D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D047309:Flavones / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C000616022:5-acetoxy-6,7,8,3',4'-pentamethoxyflavone; C000604601:5-demethylnobiletin; D047309:Flavones; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase
keywords: 3T3-L1 preadipocytes; 5-acetyloxy-6,7,8,3′,4′-pentamethoxyflavone; LKB1-AMPK pathway; high-fat diet