TY - JOUR
T1 - Dietary advanced glycation endproducts (AGEs) increase their concentration in plasma and tissues, result in inflammation and modulate gut microbial composition in mice; evidence for reversibility
AU - van Dongen, Katja C. W.
AU - Linkens, Armand M. A.
AU - Wetzels, Suzan M. W.
AU - Wouters, Kristiaan
AU - Vanmierlo, Tim
AU - van de Waarenburg, Marjo P. H.
AU - Scheijen, Jean L. J. M.
AU - de Vos, Willem M.
AU - Belzer, Clara
AU - Schalkwijk, Casper G.
N1 - Funding Information:
This work was partially supported by the SIAM Gravitation Grant 024.002.002 and 2008 Spinoza Award of the Netherlands Organization for Scientific Research to WMdV.
Funding Information:
We thank Diabetesfonds, ZonMw and Graduate school VLAG for their financial support.
Publisher Copyright:
© 2021
PY - 2021/9
Y1 - 2021/9
N2 - Scope: Dietary advanced glycation endproducts (AGEs) are associated with negative biological effects, possibly due to accumulation in plasma and tissues and through modulation of inflammation and gut microbiota. Whether these biological consequences are reversible by limiting dietary AGE intake is unknown.Methods and results: Young healthy C57BL/6 mice were fed a standard chow (n = 10) or a baked chow high AGE-diet (n = 10) (similar to 1.8-6.9 fold increased protein-bound N epsilon-(carboxymethyl)lysine (CML), N epsilon-(1-carboxyethyl) lysine (CEL), and N delta-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)) for 10 weeks or a switch diet with baked chow for 5 weeks followed by 5 weeks of standard chow (n = 10). We assessed accumulation of AGEs in plasma, kidney, and liver and measured inflammatory markers and gut microbial composition. After 10 weeks of baked chow, a substantial panel of AGEs were increased in plasma, liver, and kidney. These increases were normalized after the switch diet. The inflammatory z-score increased after the baked chow diet. Gut microbial composition differed significantly between groups, with enriched Dubosiella spp. dominating these alterations.Conclusion: A high AGE-diet led to an increase of AGEs in plasma, kidney, and liver and to more inflammation and modification of the gut microbiota. These effects were reversed or discontinued by a diet lower in AGEs.
AB - Scope: Dietary advanced glycation endproducts (AGEs) are associated with negative biological effects, possibly due to accumulation in plasma and tissues and through modulation of inflammation and gut microbiota. Whether these biological consequences are reversible by limiting dietary AGE intake is unknown.Methods and results: Young healthy C57BL/6 mice were fed a standard chow (n = 10) or a baked chow high AGE-diet (n = 10) (similar to 1.8-6.9 fold increased protein-bound N epsilon-(carboxymethyl)lysine (CML), N epsilon-(1-carboxyethyl) lysine (CEL), and N delta-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)) for 10 weeks or a switch diet with baked chow for 5 weeks followed by 5 weeks of standard chow (n = 10). We assessed accumulation of AGEs in plasma, kidney, and liver and measured inflammatory markers and gut microbial composition. After 10 weeks of baked chow, a substantial panel of AGEs were increased in plasma, liver, and kidney. These increases were normalized after the switch diet. The inflammatory z-score increased after the baked chow diet. Gut microbial composition differed significantly between groups, with enriched Dubosiella spp. dominating these alterations.Conclusion: A high AGE-diet led to an increase of AGEs in plasma, kidney, and liver and to more inflammation and modification of the gut microbiota. These effects were reversed or discontinued by a diet lower in AGEs.
KW - Dietary advanced glycation endproducts
KW - Gut microbiota
KW - 16S rRNA sequencing
KW - Ultra-performance liquid chromatography tandem mass spectrometry
KW - N-EPSILON-CARBOXYMETHYLLYSINE
KW - END-PRODUCTS
KW - INSULIN-RESISTANCE
KW - OXIDATIVE STRESS
KW - AMINO-ACIDS
KW - PROTEIN
KW - PATHWAYS
KW - RECEPTOR
KW - LIGANDS
KW - FOODS
U2 - 10.1016/j.foodres.2021.110547
DO - 10.1016/j.foodres.2021.110547
M3 - Article
C2 - 34399524
SN - 0963-9969
VL - 147
JO - Food Research International
JF - Food Research International
M1 - 110547
ER -