(-)-Epicatechin prevents TNFα-induced activation of signaling cascades involved in inflammation and insulin sensitivity in 3T3-L1 adipocytes

Arch Biochem Biophys. 2012 Nov 15;527(2):113-8. doi: 10.1016/j.abb.2012.02.019. Epub 2012 Mar 8.

Abstract

Obesity is major public health concern worldwide and obese individuals exhibit a higher risk of chronic diseases such as type 2 diabetes. Inflammation plays a significant role in metabolic regulation and mounting evidence highlight the contribution of adipose tissue to systemic inflammatory state. Food extracts with a high content of (-)-epicatechin have been found to exert systemic anti-inflammatory actions, however the anti-inflammatory actions of (-)-epicatechin on adipose tissue remain to be determined. The aim of this study was to investigate the capacity of (-)-epicatechin to prevent tumor necrosis alpha (TNFα)-induced activation of cell signals involved in inflammation and insulin resistance (NF-κB, mitogen-activated protein kinases (MAPKs), AP-1, and peroxisome proliferator activated receptor γ (PPARγ)) in differentiated white adipocytes (3T3-L1). TNFα triggered the activation of transcription factors NF-κB and AP-1, and MAPKs ERK1/2, JNK, and p38. (-)-Epicatechin caused a dose (0.5-10 μM)-dependent decrease in TNFα-mediated JNK, ERK1/2, and p-38 phosphorylation, and nuclear AP-1-DNA binding. (-)-Epicatechin also inhibited TNFα-triggered activation of the NF-κB signaling cascade, preventing TNFα-mediated p65 nuclear transport and nuclear NF-κB-DNA binding. (-)-Epicatechin also attenuated the TNFα-mediated downregulation of PPARγ expression and decreased nuclear DNA binding. Accordingly, (-)-epicatechin inhibited TNFα-mediated altered transcription of genes (MCP-1, interleukin-6, TNFα, resistin, and protein-tyrosine phosphatase 1B) involved in inflammation and insulin signaling. In conclusion, (-)-epicatechin can attenuate TNFα-mediated triggering of signaling cascades involved in inflammation and insulin resistance. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Animals
  • Antioxidants / pharmacology*
  • Catechin / pharmacology*
  • Down-Regulation / drug effects
  • Enzyme Activation / drug effects
  • Inflammation / metabolism
  • Inflammation / pathology
  • Insulin Resistance*
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • PPAR gamma / metabolism
  • Signal Transduction / drug effects*
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic / drug effects
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Antioxidants
  • Lipopolysaccharides
  • NF-kappa B
  • PPAR gamma
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • Catechin
  • Mitogen-Activated Protein Kinases