Chondroitin Sulfate from Halaelurus burgeri Skin Inhibits Hepatic Endoplasmic Reticulum Stress and Inflammation, and Regulates Gut Microbiota

Abstract

Scope

Previous study has demonstrated the chemical structure of chondroitin sulfate (CHS) from Halaelurus burgeri skin and its effects on insulin resistance. However, the precise impact of this phenomenon on endoplasmic reticulum (ER) stress and inflammation, which contribute to insulin resistance, remains unclear. This study is to investigate the impact of CHS on ER stress, inflammatory response and signaling, and gut microbiota in high-fat diet (HFD)-fed mice.

Methods and results

HFD-fed C57BL/6J mice receive dietary gavage intervention of CHS for 18 weeks. Blood, liver tissue, and feces are harvested for further investigation. Results show that CHS inhibits ER stress, accompanied by lowered blood glucose, nitric oxide (NO), reactive oxygen (ROS), and free fatty acids (FFA) levels, and increases hepatic glycogen accumulation. Moreover, hepatic inflammation is improved by CHS treatment via inactivation of Toll-like receptor 4 (TLR4) signaling and its downstream c-jun N-terminal kinase (JNK) and nuclear factor kappa B (NFκB) pathways. Additionally, CHS regulates gut microbiota, particularly the decline in the Firmicutes to Bacteroidetes ratio. CHS also lowers fecal lipopolysaccharide and elevates several fecal short chain fatty acids.

Conclusion

These findings suggest that CHS from H. burgeri skin may be an alternative functional food supplement for anti-ER stress, anti-inflammtion, and regulation of gut microbiota.