Effects of an AMP-activated protein kinase inhibitor, compound C, on adipogenic differentiation of 3T3-L1 cells

Biol Pharm Bull. 2008 Sep;31(9):1716-22. doi: 10.1248/bpb.31.1716.


The role of AMP-activated protein kinase (AMPK) in adipocyte differentiation is not completely understood. Here we reported that an AMPK inhibitor, compound C, significantly inhibited adipogenic differentiation of 3T3-L1 cells in a dose dependent manner, and this inhibitory effect was primarily effective in the initial stage of differentiation. Compound C prevented the mitotic clonal expansion (MCE) of preadipocytes, probably by inhibiting expression of CCAAT/enhancer-binding protein (C/EBP)beta and delta, and subsequently blocked the expression of C/EBPalpha and peroxisome proliferator-activated receptor (PPAR)gamma and transcriptional activation of genes that produce the adipocyte phenotype. AMPK activity was also suppressed by compound C treatment during the early phase of adipogenic differentiation, which indicated that suppressed activation of AMPK by compound C may inhibit the MCE process of preadipocytes. Our results suggest that compound C might serve as a useful molecule in both basic and clinical research on adipogenesis and as a potential lead compound for the treatment of obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / drug effects*
  • Adipogenesis / drug effects
  • Animals
  • Azo Compounds
  • Blotting, Western
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Differentiation / drug effects*
  • Clone Cells / drug effects
  • Coloring Agents
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Mice
  • Mitosis / drug effects
  • Pyrazoles / pharmacology*
  • Pyrimidines / pharmacology*
  • RNA / biosynthesis
  • RNA / isolation & purification
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism


  • Azo Compounds
  • CCAAT-Enhancer-Binding Proteins
  • Coloring Agents
  • DNA, Complementary
  • Enzyme Inhibitors
  • Pyrazoles
  • Pyrimidines
  • Transcription Factors
  • dorsomorphin
  • RNA
  • Cyclic AMP-Dependent Protein Kinases
  • oil red O