A selenium-enriched glycosaminoglycan from sturgeon cartilage: characterization and anti-metabolic syndrome potential

This study develops a novel selenium-enriched chondroitin sulfate (CSSE) from selenium-rich sturgeon cartilage that has potent multitarget activity against high-carbohydrate/high-fat diet-induced metabolic syndrome. Structural analyses (NMR/MALDI-TOF MS) confirmed Se-O-SO₃ covalent bonds (δ 78.5 ppm in ¹³C NMR) and a molecular weight of 16.8 kDa, indicating hepatic targeting with lower renal toxicity. Compared with sodium selenite, CSSE showed superior antioxidant capacity (65-80 % vs. 30-45 % DPPH scavenging) and biocompatibility (89.5 % vs. 66.4 % cell viability) (p = 0.009). In high-carbohydrate/high-fat diet (HCHF)-fed mice, CSSE markedly decreased body weight gain (-35 %), fasting glucose (-55 %), and triglyceride levels (-44 %), outperforming inorganic selenium by 2.1-3.5-fold. Mechanistically, CSSE inhibited mammalian target of rapamycin complex 1 (mTORC1) activation (32.7 % phosphorylated mammalian target of rapamycin (p-mTOR)/mammalian target of rapamycin (mTOR)), restored insulin signaling via the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt)/insulin receptor substrate 1 (IRS-1) (↑103 % phosphorylated Akt (p-Akt)/protein kinase B (Akt), and upregulated the fibroblast growth factor 21 (FGF21)/fibroblast growth factor 19 (FGF19) gut-liver axis (p = 0.028). CSSE enriched beneficial gut bacteria (e.g., Ligilactobacillus) while suppressing Allobaculum, increasing short-chain fatty acid (SCFA) production by 58.1 % and enhancing gut barrier function (↓49 % fluorescein isothiocyanate (FITC)-dextran leakage, p = 0.007). Fecal microbiota transplantation (FMT) has validated microbiota-mediated benefits. The dual antioxidant and lipid-lowering actions of CSSE, combined with its targeted delivery and safety, position it as a pioneering marine organoselenium therapy. This study also establishes a sustainable approach to transform aquaculture byproducts into precision nutraceuticals, advancing metabolic health through circular bioeconomic solutions.