Dietary Advanced Glycation Endproducts Induce an Inflammatory Response in Human Macrophages in Vitro.

Timme Van Der Lugt,Wouter Gebbink,Antje Weseler,Misha Vrolijk,Antoon Opperhuizen,Aalt Bast

doi:10.3390/nu10121868

Abstract

Advanced glycation endproducts (AGEs) can be found in protein- and sugar-rich food products processed at high temperatures, which make up a vast amount of the Western diet. The effect of AGE-rich food products on human health is not yet clear and controversy still exists due to possible contamination of samples with endotoxin and the use of endogenous formed AGEs. AGEs occur in food products, both as protein-bound and individual molecules. Which form exactly induces a pro-inflammatory effect is also unknown. In this study, we exposed human macrophage-like cells to dietary AGEs, both in a protein matrix and individual AGEs. It was ensured that all samples did not contain endotoxin concentrations > 0.06 EU/mL. The dietary AGEs induced TNF-alpha secretion of human macrophage-like cells. This effect was decreased by the addition of N(ε)-carboxymethyllysine (CML)-antibodies or a receptor for advanced glycation endproducts (RAGE) antagonist. None of the individual AGEs induce any TNF-alpha, indicating that AGEs should be bound to proteins to exert an inflammatory reaction. These findings show that dietary AGEs directly stimulate the inflammatory response of human innate immune cells and help us define the risk of regular consumption of AGE-rich food products on human health.

Highlights

During heating of food products containing protein and carbohydrates, dietary advanced glycation endproducts (AGEs) are formed via the Maillard reaction [1]
We examined the effect of individual Advanced glycation endproducts (AGEs) and whether the observed inflammatory effect was induced by activation of receptor for advanced glycation endproducts (RAGE)
To assess the effects of AGEs on human macrophage-like cells, AGEs were made in the form of glycated casein, combining casein, lactose, and glucose

Summary

Introduction

During heating of food products containing protein and carbohydrates, dietary advanced glycation endproducts (AGEs) are formed via the Maillard reaction [1]. In the Maillard reaction, the carbonyl group of a reducing sugar (sugars with a free anomeric carbon [2]) reacts with an amino moiety of an amino acid leading to reactive intermediates, the so-called Amadori products. These Amadori products form different AGEs [3]. The quantification of AGEs in food products is frequently done by antibody-based techniques [4,5], liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the preferred technique to accurately

Methods

Results

Conclusion