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J Food Drug Anal
2017 Jul 01;253:628-636. doi: 10.1016/j.jfda.2016.10.011.
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Long-chain bases from sea cucumber mitigate endoplasmic reticulum stress and inflammation in obesity mice.
Hu S
,
Wang J
,
Wang J
,
Xue C
,
Wang Y
.
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Endoplasmic reticulum (ER) stress and inflammation can induce hyperglycemia. Long-chain bases (LCBs) from sea cucumber exhibit antihyperglycemic activities. However, their effects on ER stress and inflammation are unknown. We investigated the effects of LCBs on ER stress and inflammatory response in high-fat, fructose diet-induced obesity mice. Reactive oxygen species and free fatty acids were measured. Inflammatory cytokines in serum and their mRNA expressions in epididymal adipose tissues were investigated. Hepatic ER stress-related key genes were detected. c-Jun NH2-terminal kinase and nuclear factor κB inflammatory pathways were also evaluated in the liver. Results showed that LCBs reduced serum and hepatic reactive oxygen species and free fatty acids concentrations. LCBs decreased serum proinflammatory cytokines levels, namely interleukin (IL)-1β, tumor necrosis factor-α, IL-6, macrophage inflammatory protein 1, and c-reactive protein, and increased anti-inflammatory cytokine IL-10 concentration. The mRNA and protein expressions of these cytokines in epididymal adipose tissues were regulated by LCBs as similar to their circulatory contents. LCBs inhibited phosphorylated c-Jun NH2-terminal kinase and inhibitor κ kinase β, and nuclear factor κB nuclear translocation. LCBs also inhibited mRNA expression of ER stress markers glucose regulated protein, activating transcription factor 6, double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase, and X-box binding protein 1, and phosphorylation of eukaryotic initiation factor-α and inositol requiring enzyme 1α. These results indicate that LCBs can alleviate ER stress and inflammatory response. Nutritional supplementation with LCBs may offer an adjunctive therapy for RE stress-associated inflammation.
Figure 1. The structures of long-chain bases from the sea cucumber, Cucumaria frondosa.
Figure 2. Effects of long-chain bases on inflammatory cytokines mRNA and protein expression in epididymal adipose tissue of obesity mice. (A) inflammatory cytokines mRNA; (B) tumor necrosis factor-α protein; (C) interleukin-1β protein; (D) |interleukin-10 protein. Data are expressed as mean ± standard deviation (n =12/group). Multiple comparisons were done using one-way ANOVA analysis followed by Tukey test. ##
p < 0.01 versus control; * p < 0.05, ** p < 0.01 versus high-fat fructose diet (HFFD).
Figure 3. Effects of long-chain bases on c-Jun NH2-terminal kinase and inhibitor κ kinase β/nuclear factor (NF) κB pathways in epididymal adipose tissue of obesity mice. (A) p-c-Jun NH2-terminal kinase 1 protein expression; (B) p-inhibitor κ kinase β protein expression; (C) nuclear NFκB protein expression; (D) cytoplasmic NFκB protein expression. Data are expressed as mean ± standard deviation (n =12/group). Multiple comparisons were done using one way ANOVA analysis followed by Tukey’s test. ##
p < 0.01 versus control; * p < 0.05, ** p < 0.01 versus high-fat fructose diet (HFFD).
Figure 4. Effects of long-chain bases on ER stress in the liver of obesity mice. (A) Bip mRNA expression; (B) ATF6 mRNA expression; (C) phosphoenolpyruvate kinase mRNA expression; (D) XBP1 mRNA expression; (E) p-eIF2α protein expression; (F) p-IRE1α protein expression. Data are expressed as mean ± standard deviation (n =12/group). Multiple comparisons were done using one-way ANOVA analysis followed by Tukey’s test. ##
p < 0.01 versus control; * p < 0.05, ** p < 0.01 versus high-fat fructose diet (HFFD).
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