Sulfated glycosaminoglycan from swim bladder mitigates lipid accumulation in Caenorhabditis elegans by mediating the transcription factor NHR-49

Sulfated glycosaminoglycan from swim bladder (SBG) is a marine-derived bioactive polysaccharide structurally similar to chondroitin sulfate A. This study investigates the potential of SBG in mitigating hyperlipidemia linked to lipid metabolism disorders. The results indicate that SBG significantly mitigates glucose-induced metabolic disturbances in C. elegans , including reduced fertility, shortened lifespan, elevated ROS levels, lipofuscin accumulation, and impaired antioxidant responses. Notably, at 1 mg/mL, SBG reduced triglyceride and free fatty acid levels by 56.76 % and 26.64 %, respectively ( P < 0.05), as confirmed by Oil Red O staining. At the molecular level, SBG downregulated the expression of lipid metabolism genes, such as daf-2 , mdt-15 , sbp-1 , and acs-2 . Additionally, SBG upregulated the expression of nhr-49 and daf-16 , which enhanced Δ9-desaturase activity and promoted the synthesis of monounsaturated fatty acids. The deletion of nhr-49 further confirmed that SBG regulates Δ9-desaturase through NHR-49 activation, thereby improving lipid accumulation and preserving metabolic homeostasis. • SBG extends lifespan and improves health by reducing fat accumulation in C. elegans . • SBG modulates fatty acid composition in C. elegans under a high-carbohydrate diet. • SBG significantly enhances Δ9-Fatty acid desaturase activity. • SBG activates NHR-49 to alleviate lipid metabolism disorders in C. elegans .