Oyster-derived polysaccharide modulates lipid metabolism and oxidative stress in Caenorhabditis elegans via distinct mechanisms from glucose

The physiological impact of dietary carbohydrates is intrinsically linked to their structural complexity. This study investigated how the macromolecular architecture of oyster-derived polysaccharides (OPS) elicits metabolic responses distinct from its monosaccharide building block, glucose. We hypothesized that OPS, unlike glucose, mitigates lipid accumulation and oxidative stress in <i>Caenorhabditis elegans</i> via conserved metabolic and antioxidant pathways. <i>C. elegans</i> were exposed to a range of OPS or glucose concentrations. Phenotypes assessed included lipid accumulation, antioxidant enzyme activities, reactive oxygen species (ROS) concentrations, and lifespan. Mechanistic insights were derived from qRT-PCR analysis of key genes (including daf-2, daf-16, aak-2) and global untargeted metabolomics. In contrast to glucose, which exacerbated fat storage and oxidative stress, OPS reduced triglyceride content (by 16.9 % at 50 μg/mL, <i>p</i> < 0.01) and enhanced antioxidant defenses (increased SOD activity by 28.6 %, <i>p</i> < 0.05). OPS treatment upregulated genes involved in fatty acid desaturation (fat-6, fat-7) and energy sensing (aak-2), and downregulated the insulin/IGF-1 receptor homolog daf-2. Metabolomics further demonstrated that OPS remodels metabolism toward increased unsaturated fatty acids and enhanced glutathione metabolism. This work confirms that OPS, by virtue of its complex structure, alleviates metabolic dysregulation through mechanisms divergent from glucose, primarily involving the daf-2/daf-16 and AMPK pathways. Our findings provide novel molecular insights into nutrient-specific signaling and position OPS as a promising functional ingredient for metabolic health management.