Cyanidin-3-O-Glucoside Ameliorated Hepatic Steatosis in AGEs-rich MCD Diet Induced NAFLD Mice Model via Inhibiting Endoplasmic Reticulum Stress

Non-alcoholic fatty liver disease (NAFLD) could be worsened by endogenous and exogenous advanced glycation end products (AGEs). This study investigated how exogenous AGEs exacerbate NAFLD and whether cyanidin-3-O-glucoside (C3G) as an anthocyanin could mitigate liver damage. Mice were fed with baked methionine-choline deficient (MCD) diet and treated with low or high-dose C3G gavage for six weeks. Baked MCD diet induced severe steatosis and inflammation, while C3G, particularly at high doses, reduced lipid droplet accumulation and hepatic inflammation. Proteomics revealed C3G modulated lipid metabolism, mitochondrial function, and endoplasmic reticulum pathways, and suppressed lipid synthesis enzymes such as CD36, ACC, FASN and FABP4. These findings highlight anthocyanins’ protective role in NAFLD by targeting lipid synthesis pathways, offering insights for dietary interventions and functional food development to combat metabolic liver disorders.