title: Fucosylated chondroitin sulphate from Cusumaria frondosa mitigates hepatic endoplasmic reticulum stress and inflammation in insulin resistant mice.
abstract: Endoplasmic reticulum (ER) stress-associated inflammation positively contributes to insulin resistance. It is also known that fucosylated chondroitin sulphate from Cusumaria frondosa (Cf-CHS) can mitigate insulin resistance; however, its effects on ER stress and inflammation are not well understood. Therefore, we investigated whether Cf-CHS-influenced ER stress, inflammatory response and signaling in insulin-resistant mice. Our results showed that Cf-CHS lowered serum and hepatic ROS, NO, and FFA levels. Furthermore, Cf-CHS decreased serum proinflammatory cytokines TNF-α, CRP, MIP-1, IL-1β and IL-6 concentrations as well as their hepatic mRNA expression, and increased the anti-inflammatory cytokine IL-10 levels. Moreover, Cf-CHS reduced the ER stress markers Bip, ATF6, PERK, and XBP1 mRNA or protein expression, and PERK, eIF2α, and IRE1α phosphorylation. These reductions were accompanied by a reduced activation of JNK1 and IKKβ, NFκB nuclear translocation, and IR/IRS-2 serine phosphorylation in Cf-CHS-treated mice. These findings suggested that the Cf-CHS supplementary-induced alleviation of RE stress-associated inflammation could be the mechanism responsible for its beneficial effects against insulin resistance.
authors.affiliation: Innovation Application Institute, Zhejiang Ocean University, Zhoushan, Zhejiang Province 316022, China. hushiweihai@163.com.
authors.forename: Shijie
authors.initials: S
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Shiwei
authors.initials: S
authors.lastname: Hu
authors.forename: Wendong
authors.initials: W
authors.lastname: Song
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
authors.forename: Yaning
authors.initials: Y
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
mesh_terms: D000818:Animals; D002809:Chondroitin Sulfates / Q000008:administration & dosage* / Q000302:isolation & purification; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology; D007333:Insulin Resistance; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D012616:Sea Cucumbers / Q000737:chemistry*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; C517150:fucosylated chondroitin sulfate; D016753:Interleukin-10; D002809:Chondroitin Sulfates; D051550:I-kappa B Kinase