title: Norlichexanthone isolated from fungus P16 promotes the secretion and expression of adiponectin in cultured ST-13 adipocytes.
abstract: Adiponectin, an adipose-derived protein, shows insulin-sensitizing, anti-diabetic and anti-atherogenic activities, which implies that the protein represents a potential target to improve lifestyle-related diseases like type 2 diabetes. Based on our hypothesis that agents that cause adipocyte differentiation could also act as adiponectin secretion enhancers, we screened butanol extracts of 96 fungus culture extracts for their differentiation-inducing activity in ST-13 preadipocytes. We found that the butanol extract of a fungus P16 culture extract possessed such an activity, and isolated norlichexanthone as an active compound through activity-guided fractionation. Oil red O staining showed that norlichexanthone induced adipogenesis in ST-13 cells. Its differentiation-inducing activity was supported by the observation that norlichexanthone dose-dependently increased the mRNA expression of fatty acid-binding protein and peroxisome proliferator activated receptor γ (PPARγ), markers of adipocyte differentiation. Western blot analysis demonstrated that the compound enhanced the secretion of adiponectin protein in a dose-dependent manner. An increase in mRNA expression of adiponectin was also observed in the norlichexanthone-treated ST-13 cells. Actinomycin D treatment blocked the enhancement of adiponectin mRNA expression by norlichexanthone, suggesting that it is the result of increased transcription. A luciferase reporter assay indicated that norlichexanthone was unlikely to be an agonist of PPARγ, implying that its action of mechanism might differ from those of thiazolidinediones which upregulate adiponectin expression via activation of PPARγ. These findings suggest the possibility that norlichexanthone has the potential to treat and/or prevent lifestyle-related diseases, including metabolic syndrome, type 2 diabetes, atherosclerosis and cardiovascular diseases.
authors.affiliation: Department of Nutritional Biochemistry, School of Nutrition and Dietetics, Kanagawa University of Human Services, 1-10-1 Heisei-cho, Yokosuka, Kanagawa 238-8522, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kurotobi
authors.forename: Aiko
authors.initials: A
authors.lastname: Namikawa
authors.forename: Sachi
authors.initials: S
authors.lastname: Kuranuki
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Matsuura
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sato
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Teiji
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Oikawa
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001391:Azo Compounds / Q000378:metabolism; D002460:Cell Line; D004396:Coloring Agents / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005658:Fungi / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D008019:Life Style; D051379:Mice; D058990:Molecular Targeted Therapy; D047495:PPAR gamma / Q000819:agonists* / Q000096:biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D044004:Xanthones / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; D001391:Azo Compounds; D004396:Coloring Agents; D050556:Fatty Acid-Binding Proteins; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D011500:Protein Synthesis Inhibitors; D044004:Xanthones; C568539:norlichexanthone; D003609:Dactinomycin; C011049:oil red O