Epigallocatechin-3-gallate inhibits adipogenesis through down-regulation of PPARγ and FAS expression mediated by PI3K-AKT signaling in 3T3-L1 cells

Eur J Pharmacol. 2017 Jan 15;795:134-142. doi: 10.1016/j.ejphar.2016.12.006. Epub 2016 Dec 7.

Abstract

Epigallocatechin-3-gallate (EGCG), a major component in green tea, functions as extensive bioactivities including anti-inflammation, anti-oxidation, and anti-cancer. However, little is known about its anti-adipogenesis and underlying mechanisms. The purport of this study sought to investigate effects of EGCG on 3T3-L1 preadipocyte differentiation and to explore its possible mechanisms. The 3T3-L1 cells were induced to differentiate under the condition of pro-adipogenic cocktail with or without indicated EGCG concentrations (10, 50, 100, 200µM) for 2, 4, 6 and 8 days, respectively. Also, another batch of 3T3-L1 cells was induced under the optimal EGCG concentration (100µM) with or without SC3036 (PI3K activator, 10µM) or SC79 (AKT activator, 0.5µM) for 8 days. Subsequently, the cell viability was examined by MTT assay and the cell morphology was visualized by Oil red O staining. Finally, the mRNA levels including peroxisome proliferator activated receptor γ (PPARγ) and fatty acid synthase (FAS) were detected by quantitative real time PCR, while the protein levels of PPARγ, FAS, phosphatidylinositol 3 kinase (PI3K), insulin receptor substrate1(IRS1), AKT, and p-AKT were measured by immunoblotting analysis. Our results showed that EGCG inhibited adipogenesis of 3T3-L1 preadipocyte in a concentration-dependent manner. Moreover, the inhibitory effects were reversed by SC3036 or SC79, suggesting that the inhibitory effects of EGCG are mediated by PI3K-AKT signaling to down-regulate PPARγ and FAS expression levels. The findings shed light on EGCG anti-adipogenic effects and its underlying mechanism and provide a novel preventive-therapeutic potential for obesity subjects as a compound from Chinese green tea.

Keywords: Adipocyte; Adipogenesis; Epigallocatechin-3-gallate; Peroxisome proliferator-activated receptor gamma; Phosphatidylinositol 3-kinase.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Survival / drug effects
  • Down-Regulation / drug effects*
  • Fatty Acid Synthases / genetics*
  • Insulin Receptor Substrate Proteins / metabolism
  • Mice
  • PPAR gamma / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects

Substances

  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • PPAR gamma
  • Catechin
  • epigallocatechin gallate
  • Fatty Acid Synthases
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt