Compound K, a novel ginsenoside metabolite, inhibits adipocyte differentiation in 3T3-L1 cells: involvement of angiogenesis and MMPs

Biochem Biophys Res Commun. 2012 Jun 1;422(2):263-7. doi: 10.1016/j.bbrc.2012.04.142. Epub 2012 May 3.

Abstract

Compound K, a novel ginsenoside metabolite formed by intestinal bacteria, is shown to inhibit angiogenesis and matrix metalloproteinase (MMP) activities. Since growth and development of adipose tissue are thought to require adipogenesis, angiogenesis, and extracellular matrix remodeling, we investigated whether compound K inhibits adipocyte differentiation and its potential mechanisms. Treatment of 3T3-L1 adipocytes with compound K inhibited lipid accumulation and expression of adipocyte-specific genes (i.e., PPARγ, leptin, aP2, and C/EBPα). Compound K decreased mRNA levels of angiogenic factors (i.e., VEGF-A and FGF-2) and MMPs (i.e., MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in 3T3-L1 cells. MMP-2 and MMP-9 activities were also decreased in compound K-treated cells. These results demonstrate that compound K effectively inhibited adipogenesis and that this process may be mediated in part through changes in the expression of genes involved in angiogenesis and MMP system. Thus, by suppressing adipogenesis, compound K likely has therapeutic potential for the treatment of obesity and related disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Adipogenesis / genetics
  • Animals
  • CCAAT-Enhancer-Binding Proteins / antagonists & inhibitors
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / antagonists & inhibitors
  • Fatty Acid-Binding Proteins / genetics
  • Fibroblast Growth Factor 2 / antagonists & inhibitors
  • Fibroblast Growth Factor 2 / biosynthesis
  • Gene Expression / drug effects
  • Ginsenosides / pharmacology*
  • Lipid Metabolism / drug effects
  • Matrix Metalloproteinase Inhibitors*
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / genetics
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / biosynthesis
  • Tissue Inhibitor of Metalloproteinases / metabolism
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, mouse
  • Fabp4 protein, mouse
  • Fatty Acid-Binding Proteins
  • Ginsenosides
  • Matrix Metalloproteinase Inhibitors
  • PPAR gamma
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • ginsenoside M1
  • Matrix Metalloproteinases