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阴沟肠杆菌Z0206产生的富硒胞外多糖通过AMPK/SirT1途径减轻糖尿病KKAy小鼠的脂肪炎症。

Selenium‑enriched exopolysaccharides produced by Enterobacter cloacae Z0206 alleviate adipose inflammation in diabetic KKAy mice through the AMPK/SirT1 pathway.

作者信息

Zhou Xihong, Wang Fengqin, Yang Hangxian, Chen Jingqing, Ren Yang, Yuan Zhangqin, Wang Xinxia, Wang Yizhen

机构信息

Key Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture, Zhejiang Provincial Laboratory of Feed and Animal Nutrition, Institute of Feed Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.

出版信息

Mol Med Rep. 2014 Feb;9(2):683-8. doi: 10.3892/mmr.2013.1859. Epub 2013 Dec 11.

Abstract

Polysaccharides belong to a structurally diverse class of macromolecules, with the necessary flexibility for the precise regulatory mechanisms and high capacity for carrying biological information. On the basis of a previous study regarding the administration of selenium-enriched exopolysaccharides (Se-ECZ-EPS) produced by Enterobacter cloacae (E. cloacae) Z0206 which resulted in a reduction of blood glucose levels and showed significant anti-inflammatory and anti-diabetic effects, the present study was conducted to evaluate the effects and mechanism of EPS on the alleviation of fat inflammation in high-fat-diet (HFD) induced-diabetic KKAy mice. The HFD induced-diabetic KKAy mice were gavaged once daily with EPS (0.2 mg/g body weight) or distilled water, while the C57BL/6J mice were gavaged with distilled water. Six weeks later visceral adipose tissue (VAT) was collected for quantified polymerase chain reaction (qPCR) and western blot (WB) analysis. The results showed that following supplementation with EPS, interleukin (IL) 6, IL1β and tumor necrosis factor (TNF) α mRNA expression in VAT were significantly reduced, while Glut4, pAMPK and SirT1 protein expression were markedly increased when compared with KKAy mice gavaged with water. Furthermore, ATGL and HSL mRNA were also significantly decreased. Subsequently, 3T3-L1 adipocytes were treated with insulin to induce insulin resistance to determine the mechanism by which EPS affects inflammation. Following the treatment of adipocytes with 100 nM insulin for 8 h, IL6 and TNFα mRNA expression were significantly increased, while the content of glucose uptake and Glut4 protein expression were significantly decreased. When treated with 100 nM insulin and 0.1 mg/ml EPS, no significant change in IL6 and TNFα mRNA expression or glucose uptake were observed. However, when SirT1‑siRNA or AMPKα1-siRNA was transfected into the 3T3-L1 adipocytes prior to treatment with insulin and EPS, there was a significant increase in IL6 and TNFα mRNA abundance. In conclusion, VAT inflammation and lipolysis in HFD-induced KKAy mice were significantly decreased following EPS usage. Moreover, EPS may alleviate VAT inflammation primarily through the AMPK/SirT1 pathway.

摘要

多糖属于一类结构多样的大分子,具有精确调控机制所需的灵活性以及携带生物信息的高容量。基于先前一项关于阴沟肠杆菌(E. cloacae)Z0206产生的富硒胞外多糖(Se-ECZ-EPS)给药的研究,该研究导致血糖水平降低并显示出显著的抗炎和抗糖尿病作用,本研究旨在评估EPS对高脂饮食(HFD)诱导的糖尿病KKAy小鼠脂肪炎症缓解的影响及机制。将HFD诱导的糖尿病KKAy小鼠每天一次灌胃给予EPS(0.2 mg/g体重)或蒸馏水,而C57BL/6J小鼠灌胃给予蒸馏水。六周后,收集内脏脂肪组织(VAT)用于定量聚合酶链反应(qPCR)和蛋白质免疫印迹(WB)分析。结果表明,与灌胃水的KKAy小鼠相比,补充EPS后,VAT中白细胞介素(IL)6、IL1β和肿瘤坏死因子(TNF)α的mRNA表达显著降低,而Glut4、pAMPK和SirT1蛋白表达明显增加。此外,ATGL和HSL的mRNA也显著降低。随后,用胰岛素处理3T3-L1脂肪细胞以诱导胰岛素抵抗,以确定EPS影响炎症的机制。用100 nM胰岛素处理脂肪细胞8小时后,IL6和TNFα的mRNA表达显著增加,而葡萄糖摄取量和Glut4蛋白表达显著降低。当用100 nM胰岛素和0.1 mg/ml EPS处理时,未观察到IL6和TNFα的mRNA表达或葡萄糖摄取有显著变化。然而,在用胰岛素和EPS处理之前,将SirT1-siRNA或AMPKα1-siRNA转染到3T3-L1脂肪细胞中时,IL6和TNFα的mRNA丰度显著增加。总之,使用EPS后,HFD诱导的KKAy小鼠的VAT炎症和脂肪分解显著降低。此外,EPS可能主要通过AMPK/SirT1途径减轻VAT炎症。

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