In mice fed a high-fat diet, supplementation with fructose or glucose increases hepatic oxidative stress, reduces expression of antioxidant enzymes SOD-2, HO-1, and catalase, and elevates lipid peroxidation measured as TBARS, indicating a shared mechanism of metabolic toxicity leading to liver injury.

Excess fat and sugar in the liver overwhelm the cell's ability to process them, leading to toxic fat buildup that damages mitochondria and triggers harmful molecules called reactive oxygen species. The liver tries to fight back by activating its antioxidant system, but constant stress shuts down key protective enzymes. Without these defenses, the reactive molecules attack and break down fats in the liver, causing irreversible damage and inflammation that leads to cell death and scarring.