Curcumin ameliorates high-glucose-induced lipid accumulation in HepG2 cells via AMPK activation and mTOR suppression.

A typical consequence of diabetes is diabetes-associated non-alcoholic fatty liver disease (D-NAFLD), which is defined by excessive hepatic lipid buildup brought on by insulin resistance and chronic hyperglycemia. In this study, we established a high-glucose-induced HepG2 cell model to mimic the diabetic hepatic environment and examine how curcumin protects against liver fat accumulation caused by high blood sugar. Oil Red O staining and Immunoblotting analysis demonstrated that curcumin significantly reduced lipid accumulation in HepG2 cells under high-glucose conditions. To explore the underlying molecular mechanisms, we applied bioinformatic analysis in diabetic patients with and without NAFLD and identified the AMPK/mTOR pathway as a critical regulator of hepatic lipid metabolism. Additionally, molecular docking studies showed that curcumin has a high affinity for binding to AMPK (-8.1 kcal/mol). Western blot analysis confirmed that curcumin alleviates lipid accumulation via AMPK activation and mTOR signaling inhibition. To verify the essential role of AMPK in this process, we employed an AMPK inhibitor, which abolished curcumin's protective effects. These findings indicate that curcumin attenuates hyperglycemia-induced hepatic steatosis via AMPK activation and mTOR suppression, highlighting its potential therapeutic value in the treatment of D-NAFLD.