Nε-(Carboxymethyl)lysine (CML) Promotes Disorders of Glucose and Lipid Metabolism in Human Hepatic LO2 Cells

Advanced glycation end products (AGEs) are widely found in processed foods; their free fractions could significantly affect cellular glucose and lipid metabolism, but this mechanism remains poorly understood. We selected Nε-(carboxymethyl)lysine (CML) as a representative free AGE to study the biochemical processes involved in glucose metabolism, lipid synthesis, and catabolism in human LO2 cells. A combination of biochemical, metabolic flux, and comparative experiments revealed that the mechanism of CML intervention in glucose metabolism mainly involves promoting the dephosphorylation of glucose 6-phosphate and inhibiting the conversion of cis-aconitate to isocitrate in the Krebs cycle. Regarding lipid metabolism, CML combined with high-glucose stimulation synergistically promoted de novo lipogenesis, and CML also promoted fatty acid β-oxidation. These results provide constructive insights into the mechanisms and targets of the imbalance in cellular glucose and lipid metabolism induced by dietary AGEs.