Neoagarooligosaccharides improve non-alcoholic fatty liver disease by modulating lipid metabolism and Nrf2-related pathways

Neoagarooligosaccharides (NAO), polysaccharides derived from seaweed, exhibit anti-obesity, hepatoprotective, and anti-inflammatory properties. However, their effects on non-alcoholic fatty liver disease (NAFLD) remain underexplored. This study investigates the impact of NAO on lipid accumulation and oxidative stress in free fatty acid (FFA)-treated HepG2 cells and high-fat diet-fed mice. NAO treatment significantly reduced triglyceride and total cholesterol levels, inhibited lipid accumulation (assessed via Oil Red O staining), and lowered liver enzyme levels. NAO also suppressed oxidative stress by enhancing antioxidant enzyme activity and reducing malondialdehyde levels. Real-time PCR and Western blot analyses revealed that NAO modulated lipid transporters, increased AMPK and β-oxidation, and reduced de novo lipogenesis. It also regulated the PI3K/AKT/Nrf2 pathway, suggesting its role in antioxidant defense. These findings highlight NAO's potential as a promising natural compound for developing effective and less toxic therapeutic interventions for NAFLD by mitigating lipid accumulation and oxidative stress.