Scope: Epidemiologic studies indicate significant contributions of thermally processed diets to the risk for diabetes and its related renal complications, but the mechanisms relating diet to disease remain unclear. This study evaluates the effects of the diet differ only in the content of advanced glycation end-products (AGEs) on early diabetes in Leprdb/db mice.
Methods and results: High AGEs diet (60 mg CML per kg protein) is fed to mice for 8 weeks. Dietary AGEs associated with diabetic features, including hyperglycemia, insulin resistance, and increased mRNA expression of renal chemokines, CCL3 and CXC3L1 are found. Untargeted metabolomics reveal that the high AGEs diet inhibits carbohydrate catabolism and promotes lipid anabolism. Additionally, the high AGEs diet alters the composition of the gut microbiota and indirectly affects the carbohydrate metabolism by altering the plasma levels of glyceraldehyde and pyruvate. However, switching to the lower AGEs diet can relieve most of the symptoms except microbiota composition.
Conclusion: The results indicate that dietary AGEs exposure intervenes in the development of diabetes through modulating the carbohydrate and lipid metabolism, and critically, switching to the lower AGEs diet arrested or reversed diabetes progression. A light-processing dietary intervention that helps to arrest early diabetes is suggested.
Keywords: Nε-carboxymethyl-lysine; advanced glycation end-products; diabetes; metabolomics; microbiome.
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