Epicatechin downregulates adipose tissue CCL19 expression and thereby ameliorates diet-induced obesity and insulin resistance

Nutr Metab Cardiovasc Dis. 2017 Mar;27(3):249-259. doi: 10.1016/j.numecd.2016.11.008. Epub 2016 Nov 23.

Abstract

Background and aims: Epicatechin (EC) intake has been suggested to be beneficial for the prevention of cardiovascular disorders, and it is well known that adipose tissue inflammation is one of the major risk factors for coronary heart diseases. The purpose of the present study was to determine the in vitro and in vivo effects of EC on adipose tissue inflammation and obesity.

Methods and results: DNA microarray analysis was performed to evaluate the effects of EC on gene expression in adipocytes co-cultured with bacterial endotoxin-stimulated macrophages. To determine the in vivo effects of the catechin, C57BL/6 mice were fed either a high-fat diet (HFD) or HFD combined with EC, and metabolic changes were observed EC suppressed the expression of many inflammatory genes in the adipocytes co-cultured with endotoxin-stimulated macrophages. Specifically, EC markedly suppressed chemokine (CC motif) ligand 19 (CCL19) expression. The target cell of EC appeared to macrophages. The in vivo study indicated that mice fed the EC-supplemented HFD were protected from diet-induced obesity and insulin resistance. Accordingly, the expression levels of genes associated with inflammation in adipose tissue and in the liver were downregulated in this group of mice.

Conclusions: EC exerts beneficial effects for the prevention of adipose tissue inflammation and insulin resistance. Since we previously reported that mice deficient in the CCL19 receptor were protected from diet-induced obesity and insulin resistance, it can be concluded that the beneficial effects of EC could be mediated, at least in part, by marked suppression of CCL19 expression.

Keywords: Adipocyte–macrophage interaction; Adipokine; CCL19; Epicatechin; Inflammation.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Catechin / pharmacology*
  • Chemokine CCL19 / genetics
  • Chemokine CCL19 / metabolism*
  • Coculture Techniques
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Down-Regulation
  • Insulin Resistance*
  • Macrophage Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Obesity / etiology
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / prevention & control*
  • Panniculitis / etiology
  • Panniculitis / genetics
  • Panniculitis / metabolism
  • Panniculitis / prevention & control*
  • RAW 264.7 Cells
  • Time Factors

Substances

  • Anti-Inflammatory Agents
  • Ccl19 protein, mouse
  • Chemokine CCL19
  • Catechin