Figure 1.

Hypothesis on how dietary Advanced Glycation End products (AGEs) affect intestinal epithelial cells under homeostatic (left panel) and inflammatory conditions (right panel), based on results of in vivo rodent studies. Under homeostatic conditions, dietary AGEs seem to increase intestinal permeability independent from inflammation, while RAGE is expressed on the lateral side of epithelial cells underneath the tight junctions. Since especially protein-bound AGEs have affinity for RAGE, it is unlikely that this effect is induced in a RAGE-dependent manner as cellular arrangements under homeostatic conditions are too tight for proteins to pass the barrier paracellularly. It is more likely that the effect is induced by intracellular signaling of AGEs, being absorbed via passive diffusion, active transport or endocytosis. In case of inflammation, the intestinal barrier function is hampered. Therefore, in addition to the intracellular signaling mentioned above, protein-bound AGEs would be able to interact with RAGE, which is expressed on lateral as well as basolateral side under these conditions. Although data is limited, AGEs seem to have a protective effect on inflammation, suggesting that they would act as a partial agonist or antagonist on RAGE for NFκB activation or enhance scavenging or RAGE agonists by exaggerating RAGE shedding. Figure created with BioRender.com.