Fucosylated chondroitin sulphate from sea cucumber reduces hepatic endoplasmic reticulum stress-associated inflammation in obesity mice

• ER stress-associated inflammation is reduced by Am-CHS.
• Am-CHS decreases ROS, NO, and FFA levels and regulates inflammatory cytokines.
• Bip-triggered PERK/eIF2α, IRE1/XBP1, and ATF6 signalling was inactivated by Am-CHS.
• Am-CHS alleviates inflammation via inactivation of JNK and IKK-β/NFκB signalling.
• Am-CHS is a novel functional factor for ER stress-associated inflammation.

Endoplasmic reticulum (ER) stress-associated inflammation positively induces many diseases, including insulin resistance. Fucosylated chondroitin sulphate from Acaudina molpadioides (Am-CHS) can mitigate insulin resistance. However, its effects on ER stress and inflammation are unclear. We investigated whether Am-CHS influenced ER stress, inflammatory cytokines, and JNK and IKKβ/NFκB pathways in insulin resistant mice. Am-CHS lowered serum and hepatic ROS, NO, and FFA levels. Meanwhile, Am-CHS decreased serum proinflammatory cytokines TNF-α, CRP, MIP-1, IL-1β and IL-6 concentrations and their hepatic mRNA expression, and increased anti-inflammatory cytokine IL-10 levels. Am-CHS reduced ER stress markers Bip, ATF6, PERK, and XBP1 mRNA or protein expression, and PERK, eIF2α, and IRE1α phosphorylation. These reductions were accompanied by reduced JNK1 and IKKβ activation, NFκB nuclear translocation, and IR/IRS-2 serine phosphorylation in Am-CHS-treated mice. These findings suggest that Am-CHS could be an alternative against inflammation and ER stress as a functional food ingredient and natural health product.