Distinct effects of methylglyoxal-derived hydroimidazolone 1, N-carboxyethyllysine, and an advanced glycation end product-rich diet on lipid metabolism, gut microbiota, and secondary bile acids in high-fat diet-induced obese mice.

Dietary advanced glycation end products (dAGEs) are implicated in oxidative stress, inflammation, and metabolic dysregulation. This study investigated the impact of methylglyoxal-derived hydroimidazolone 1 (MG-H), N-carboxyethyllysine (CEL), and a heated diet on metabolic health and gut microbiota in a high-fat diet (HFD)-induced obese mouse model. CEL and MG-H significantly reduced final body weight in HFD-fed mice, whereas the heated diet increased it. Both MG-H and the heated diet caused significant hepatic accumulation of arginine-derived AGEs, with minimal lysine-derived deposition. Untargeted metabolomics and targeted lipidomics showed that MG-H and the heated diet altered levels of lysophosphatidylcholine species, phenylalanine, and fatty acids. 16S rRNA sequencing showed that all treatments modified gut microbiota composition, with MG-H and CEL notably increasing Verrucomicrobiaceae and Erysipelotrichaceae, and elevated secondary bile acid levels. These metabolic and microbial changes correlated with lipid metabolism disturbances. Overall, these findings demonstrate that dAGEs differentially impact obesity via host-microbiota-metabolism interactions.