Indole Derivatives Isolated from Brown Alga Sargassum thunbergii Inhibit Adipogenesis through AMPK Activation in 3T3-L1 Preadipocytes

Mar Drugs. 2017 Apr 12;15(4):119. doi: 10.3390/md15040119.

Abstract

Seaweed, a popular and abundant food ingredient mainly consumed in Asian countries, is a good source of bioactive compounds with anti-obesity effects. However, the anti-obesity effects of Sargassum thunbergii have not yet been established. In this study, we isolated six indole derivatives (STCs)-indole-2-carboxaldehyde (STC-1), indole-3-carboxaldehyde (STC-2), indole-4-carboxaldehyde (STC-3), indole-5-carboxaldehyde (STC-4), indole-6-carboxaldehyde (STC-5), and indole-7-carboxaldehyde (STC-6)-from S. thunbergii and evaluated their inhibitory effects on adipocyte differentiation in 3T3-L1 cells. We found that STC-1 and STC-5 resulted in non-toxic inhibition of the differentiation of 3T3-L1 adipocytes and thus selected these compounds for further study. STC-1 and STC-5 significantly inhibited lipid accumulation and downregulated the expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1c (SREBP-1c) in a dose-dependent manner. The specific mechanism mediating the effects of STC-1 and STC-5 was shown to be AMP-activated protein kinase (AMPK) activation. Our results demonstrated the inhibitory effect of STC-1 and STC-5 on adipogenesis through the activation of the AMPK signal pathway. Together, these findings suggested that STC-1 and STC-5 may be effective candidates for the prevention of obesity or obesity-related diseases.

Keywords: Sargassum thunbergii; adipocyte; anti-obesity effect; indole derivatives.

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / metabolism*
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Anti-Obesity Agents / pharmacology
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Differentiation / drug effects
  • Cell Line
  • Down-Regulation / drug effects
  • Indoles / pharmacology*
  • Mice
  • Obesity / drug therapy
  • Obesity / metabolism
  • PPAR gamma / metabolism
  • Phaeophyceae / chemistry*
  • Sargassum / chemistry*
  • Seaweed / drug effects
  • Signal Transduction / drug effects

Substances

  • Anti-Obesity Agents
  • CCAAT-Enhancer-Binding Proteins
  • Indoles
  • PPAR gamma
  • AMP-Activated Protein Kinases