Protocatechuic Acid Ameliorates High Fat Diet‐Induced Obesity and Insulin Resistance in Mice

Scope Insulin resistance is a common feature of obesity and type 2 diabetes and partly results from an imbalance between food intake and energy expenditure. Therefore, efficient and safe insulin resistance treatment therapies are warranted. This work is aim to access the impact of protocatechuic acid (PCA), a catechol‐type O‐diphenol phenolic acid, in high fat diet (HFD)‐induced glucose, and lipid dysregulation. Methods and results Five‐week‐old male C57BL/6 mice are fed with HFD for 4 weeks and then are randomly divided into two cohorts: one cohort feed with HFD is free access to sterile water for 4 weeks, another cohort is free access to PCA‐containing water (2.7 mM) for 4 weeks with HFD. In this study, using a hyperinsulinemic–euglycemic mouse clamp, it is showed that PCA‐treated mice display improved systemic insulin resistance via enhanced fatty acid mobilization and utilization, thereby reducing ectopic lipid accumulation and promoting hepatic and peripheral insulin action. Conclusions This study provides insights on the potent pharmacological effects of PCA from food sources on improving high fat diet (HFD)‐induced whole‐body insulin resistance and type 2 diabetes.