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Title: Inhibition of adipogenesis and leptin production in 3T3-L1 adipocytes by a derivative of meridianin C

Highlights: • Compound 7b, a meridianin C derivative, inhibits adipogenesis. • Compound 7b inhibits C/EBP-α, PPAR-γ, FAS, STAT-3, and STAT-5 in 3T3-L1 adipocytes. • Compound 7b inhibits leptin, but not adiponectin, expression in 3T3-L1 adipocytes. • Compound 7b thus may have therapeutic potential against obesity. - 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 bymore » down-regulating expressions and/or phosphorylations of C/EBP-α, PPAR-γ, FAS, STAT-3 and STAT-5.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [4] ;  [5] ;  [1]
  1. Department of Molecular Medicine, College of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701 (Korea, Republic of)
  2. Department of Microbiology, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Nam-gu, Daegu 705-717 (Korea, Republic of)
  3. Division of Life Science, Korea Basic Science Institute, 169-148 Gwahakro, Yuseong-gu, Daejeon 305-333 (Korea, Republic of)
  4. Department of Chemistry, College of Natural Sciences, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701 (Korea, Republic of)
  5. Department of Immunology, College of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416778
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 452; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADENOSINE; ALKALOIDS; AMP; CARBOXYLIC ACIDS; HUMAN POPULATIONS; INHIBITION; LEPTIN; LEUKEMIA; LEUKEMIA VIRUSES; LIPIDS; METABOLIC DISEASES; PHOSPHORYLATION; PHOSPHOTRANSFERASES; RECEPTORS; TRANSCRIPTION; TRANSDUCERS