title: Illudins C2 and C3 stimulate lipolysis in 3T3-L1 adipocytes and suppress adipogenesis in 3T3-L1 preadipocytes.
abstract: The secondary metabolites illudins C2 (1) and C3 (2), obtained from the culture broth of Coprinus atramentarius, have been shown to possess antimicrobial activity. In the present study, we discovered novel biological activities of 1 and 2 in lipolysis of differentiated 3T3-L1 adipocytes and adipogenesis of 3T3-L1 preadipocytes. Compounds 1 and 2 exhibit a dose-dependent increase in glycerol release and thereby reduce intracellular lipid accumulation. The stimulatory effects of 1 and 2 on lipolysis are prevented by cAMP-dependent protein kinase (PKA) and extracellular signal-regulated kinase (ERK) inhibitors. Compounds 1 and 2 down-regulated perilipin and also affected the mRNA and protein levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). However, 1 and 2 treatment leads to a significant increase in PKA-mediated phosphorylation of HSL at S563 and S660. In addition, 1 and 2 treatment in 3T3-L1 preadipocytes induces down-regulation of the critical transcription factors, CCAAT/enhancer binding protein α and β (C/EBPα and C/EBPβ), and peroxisome proliferator activated receptor γ (PPARγ), which are required for adipogenesis, and accordingly inhibits adipogenesis. These results suggest that 1 and 2 might be useful for treating obesity due to their modulatory effects on fat by affecting adipocyte differentiation and fat mobilization.
authors.affiliation: World Class Institute (WCI) Center, Korea Research Institute of Bioscience and Biotechnology , 30 Yeongudanjiro, Ochang, Cheongwon, Chungbuk 363-883, Korea.
authors.forename: Sun-Ok
authors.initials: SO
authors.lastname: Kim
authors.forename: Krisada
authors.initials: K
authors.lastname: Sakchaisri
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Asami
authors.forename: In-Ja
authors.initials: IJ
authors.lastname: Ryoo
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Choo
authors.forename: Ick-Dong
authors.initials: ID
authors.lastname: Yoo
authors.forename: Nak-Kyun
authors.initials: NK
authors.lastname: Soung
authors.forename: Young Sang
authors.initials: YS
authors.lastname: Kim
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Jang
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000187:drug effects*; D003302:Coprinus / Q000737:chemistry*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005990:Glycerol / Q000032:analysis / Q000378:metabolism; D008049:Lipase / Q000032:analysis / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy; D047495:PPAR gamma / Q000378:metabolism*; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000217:Acyltransferases
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D005990:Glycerol; D008049:Lipase; D047495:PPAR gamma; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C101777:illudin C2; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases