Dietary dicarbonyl compounds exacerbated immune-dysfunction and hepatic oxidative stress under high-fat diet in vivo

High-fat diets (HFDs) predispose to obesity and liver dysfunctions, and α-dicarbonyl compounds (α-DCs) present in highly processed foods are also implicated in relevant pathological processes. However, the synergistic harmful effects of α-DCs co-administered with HFDs remain to be elucidated. In this study, 6-week-old C57BL/6 mice were fed with a HFD co-administered with 0.5% methylglyoxal (MGO)/glyoxal (GO) in water for 8 weeks, and multi-omics approaches were employed to investigate the underlying toxicity mechanisms. The results demonstrated that the MGO intervention with a HFD led to an increased body weight and blood glucose level, accompanied by the biological accumulation of α-DCs and carboxymethyl-lysine, as well as elevated serum levels of inflammatory markers including IL-1β, IL-6, and MIP-1α. Notably, hepatic lesions were observed in the MGO group under HFD conditions, concomitant with elevated levels of malondialdehyde. Transcriptomic analysis revealed enrichment of pathways and differentially expressed genes (DEGs) associated with inflammation and oxidative stress in the liver. Furthermore, α-DC intervention exacerbated gut microbial dysbiosis in the context of a HFD, and through Spearman correlation analysis, the dominant genera such as