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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\u2010fat diet (HFD)\u2010fed mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>HFD\u2010fed 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\u2010like receptor 4 (TLR4) signaling and its downstream c\u2010jun N\u2010terminal kinase (JNK) and nuclear factor kappa B (NF\u03baB) 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that CHS from <jats:italic>H. burgeri<\/jats:italic> skin may be an alternative functional food supplement for anti\u2010ER stress, anti\u2010inflammtion, and regulation of gut microbiota.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202400501","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T08:20:32Z","timestamp":1727425232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chondroitin Sulfate from <i>Halaelurus burgeri<\/i> Skin Inhibits Hepatic Endoplasmic Reticulum Stress and Inflammation, and Regulates Gut Microbiota"],"prefix":"10.1002","volume":"68","author":[{"given":"Zhaocai","family":"Ren","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Maine Aquaculture Zhejiang Ocean University  Zhoushan 316022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang","family":"Gao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Maine Aquaculture Zhejiang Ocean University  Zhoushan 316022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5342-5609","authenticated-orcid":false,"given":"Shiwei","family":"Hu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Maine Aquaculture Zhejiang Ocean University  Zhoushan 316022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sichun","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Maine Aquaculture Zhejiang Ocean University  Zhoushan 316022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Maine Aquaculture Zhejiang Ocean University  Zhoushan 316022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaming","family":"Ge","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Maine Aquaculture Zhejiang Ocean University  Zhoushan 316022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0286726"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2022.104954"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3FO00089C"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.012"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06663-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102569"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.67722"},{"key":"e_1_2_9_8_1","volume":"1","author":"Chen Y.","year":"2022","journal-title":"Oxid Med Cell Longev"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","unstructured":"S. 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