A natural heparinoid from Halaelurus burger skin: Structures and regulation of insulin resistance

Glycosaminoglycans (GAGs) have garnered increasing attention for improving insulin resistance. In this study, a novel heparinoid, classified under GAGs, was successfully isolated and purified from the skin of Halaelurus burgeri (Hep-hb). The heparinoid exhibited a molecular weight of 258.817 kDa and consisted primarily of GlcpN and GlcpNAc. The structure of Hep-hb was thoroughly characterized using FT-IR, GC-MS, and NMR techniques. It was determined that the backbone is composed of repeated units: [→3)-β-D-GlcpNAc(2S)-(1 → 4)-β-D-GlcpA-(1 → 3)-β-D-GlcpNAc-(1]_n→. Additionally, our study aimed to uncover the underlying therapeutic mechanisms of Hep-hb in insulin-resistant mice by analyzing cytokine levels in serum and investigating lipid metabolism differences in vivo. Biochemical indicators were applied to assess model validity and treatment efficacy in mice fed a high-fat diet. Oral administration of Hep-hb demonstrated therapeutic effects on insulin-resistant mice by inhibiting body weight gain and improving lipid metabolism through enhanced thermogenesis. Gut microbial sequencing revealed that treatment with Hep-hb increased intestinal flora diversity while selectively enriching key species such as Bacteroides, Lactobacillus, Lachnospiraceae, and Akkermansia，and decreasing Helicobacter, Oscillospiraceae, Colidextribacter, and Erysipeloterichaceae. These findings suggest that Hep-hb holds significant potential as a natural functional food for preventing hyperglycemia and insulin resistance.