| Summary: | In this study, the effects of Holothuria tubulosa sea cucumber (Ht- FUC) with different molecular weight (Ht, Ht-1, Ht-2, Ht-3) on β cell apoptosis induced by high-fat-high-sucrose diet (HFD) in male C57BL/6J mice were investigated. After intervention with Ht-FUC (60 mg/kg body weight) for 16 weeks, results showed that different Ht-FUC could significantly decrease blood glucose and insulin levels, and reduce the burden of islet β cell secretion (P < 0.05). Notably, Ht-FUC significantly decreased serum free fatty acid (FFA) levels and lightened vacuolarization of islet. The results of qPCR and western blot showed that Ht-FUC suppressed PERK/CHOP and IRE1α/JNK pathways to inhibit ERS induced by FFA (P < 0.05). And then downregulated the expression of key genes in mitochondrial apoptosis pathway such as Bid, Bax, cytochrome c, caspase9 and caspase3 (P < 0.05), but didn’t affect Fas/FasL pathway, ultimately blocked the “FFA-endoplasmic reticulum stress (ERS)-apoptosis” cascade. All the results showed structure-activity relationship consistently and Ht-2 (196KDa) with short chain conformation played the best effect (P < 0.05).
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