title: Inhibition of adipogenesis and leptin production in 3T3-L1 adipocytes by a derivative of meridianin C.
abstract: Meridianin C, a marine alkaloid, is a potent protein kinase inhibitor and has anti-cancer activity. We have recently developed a series of meridianin C derivatives (compound 7a-7j) and reported their proviral integration Moloney Murine Leukemia Virus (pim) kinases' inhibitory and anti-proliferative effects on human leukemia cells. Here we investigated the effect of these meridianin C derivatives on adipogenesis. Strikingly, among the derivatives tested, compound 7b most strongly inhibited lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. However, meridianin C treatment was largely cytotoxic to 3T3-L1 adipocytes. On mechanistic levels, compound 7b reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), and fatty acid synthase (FAS) but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during adipocyte differentiation. Moreover, compound 7b repressed leptin, but not adiponectin, expression during adipocyte differentiation. Collectively, these findings demonstrate that a meridianin C derivative inhibits adipogenesis by down-regulating expressions and/or phosphorylations of C/EBP-α, PPAR-γ, FAS, STAT-3 and STAT-5.
authors.affiliation: Department of Molecular Medicine, College of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701, Republic of Korea.
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Microbiology, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Nam-gu, Daegu 705-717, Republic of Korea.
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Division of Life Science, Korea Basic Science Institute, 169-148 Gwahakro, Yuseong-gu, Daejeon 305-333, Republic of Korea.
authors.forename: Jong-Soon
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Chemistry, College of Natural Sciences, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701, Republic of Korea.
authors.forename: Victor Sukbong
authors.initials: VS
authors.lastname: Hong
authors.affiliation: Department of Chemistry, College of Natural Sciences, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701, Republic of Korea. Electronic address: jinho@gw.kmu.ac.kr.
authors.forename: Jinho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Immunology, College of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701, Republic of Korea. Electronic address: j303nih@dsmc.or.kr.
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Molecular Medicine, College of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701, Republic of Korea. Electronic address: jangbc123@gw.kmu.ac.kr.
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D026121:Indole Alkaloids / Q000494:pharmacology*; D020738:Leptin / Q000096:biosynthesis*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D051379:Mice
chemical_list: D026121:Indole Alkaloids; D020738:Leptin
keywords: Adipogenesis; C/EBP-α; Meridianin C derivative; PPAR-γ; STAT-3/5