Polyphenols reverse hyperglycemia-induced adipocyte dysfunction: A Metabolomic and Lipidomic study of efficacy.

Hyperglycemia leads to metabolic dysfunction in human adipocytes, characterized by decreased AKT phosphorylation, downregulation of glycolysis, TCA cycle, and amino acid metabolism, as well as altered lipid profiles. This study aimed to elucidate these metabolic alterations and evaluate the potential therapeutic effects of selected polyphenols. Comprehensive metabolic profiling revealed profound disruptions, including impaired carbon metabolism, amino acids, and lipids associated with obesity. Importantly, treatment with polyphenols, particularly verbascoside and ferulic acid, effectively mitigated these metabolic disturbances, restoring adipocyte homeostasis. The polyphenols increased metabolites from carbon metabolism and amino acids, improving glycolysis, the TCA cycle, and related pathways. They also modulated lipid profiles that are negatively associated with obesity and related diseases. These findings provide valuable insights into the metabolic pathways underlying adipocyte dysfunction in hyperglycemia and highlight the therapeutic potential of polyphenols in ameliorating metabolic disorders.