TRIM31 Deficiency Is Associated with Impaired Glucose Metabolism and Disrupted Gut Microbiota in Mice.

TRIM31 Deficiency Is Associated with Impaired Glucose Metabolism and Disrupted Gut Microbiota in Mice.
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TRIM31 缺乏与小鼠葡萄糖代谢受损和肠道微生物群破坏有关

DOI:
10.3389/fphys.2018.00024
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发表时间:
2018
影响因子:
4
通讯作者:
Zhang Y
Zhang Y
中科院分区:
医学2区
文献类型:
--
作者:
Cheng J;Xue F;Zhang M;Cheng C;Qiao L;Ma J;Sui W;Xu X;Gao C;Hao P;Zhang M;Zhang Y

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含三方基序的蛋白31(TRIM31)是三方基序家族中的一种E3泛素连接酶,在天然免疫应答中发挥重要作用。它可以降低核苷酸结合的寡聚结构域样受体(NLR)家族含有3(NLRP3)炎症体的吡喃结构域的活性。然而,关于TRIM31基因缺陷小鼠的葡萄糖代谢健康的信息很少,关于TRIM31基因缺陷小鼠肠道微生物区系的研究也很有限。因此,我们旨在比较TRIM31−/−小鼠和野生型(WT)小鼠的葡萄糖代谢参数、肠道微生物区系组成和炎症细胞因子水平,并进一步研究特定的肠道微生物区系分类是否与TRIM31基因缺陷小鼠的特定代谢参数和炎症细胞因子相关。−/−小鼠表现出葡萄糖耐受和胰岛素抵抗,肠道微生物区系组成有显著差异,其特征是普罗瓦泰科和韦龙科的丰度增加。−/−小鼠糖代谢受损后,血清肿瘤坏死因子-α和白介素1-α水平升高,盲肠肿瘤坏死因子-β、白介素1-、半胱氨酸天冬氨酸氨基转移酶-1和白介素RP3表达上调。此外,在TRIM31−/−小鼠中观察到p-IRS-1/IRS-1蛋白表达增加,Akt Thr308磷酸化降低。普氏菌科的丰度与盲肠IL-1的β表达呈正相关,而韦氏菌科与较高的α表达和血清胰岛素浓度呈正相关。总而言之,我们的研究在表明TRIM31缺乏与小鼠的葡萄糖代谢受损和肠道微生物区系紊乱有关方面是新颖的。本研究为研究TRIM31缺乏症与糖代谢异常的发生发展之间的潜在关系奠定了理论基础。
Tripartite motif-containing protein 31 (TRIM31), an E3 ubiquitin ligase of the tripartite motif family, plays an important role in the innate immune response. It can reduce the activity of the nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. However, little information is about glucose metabolic health of TRIM31-deficient mice, and investigations about gut microbiota in TRIM31-deficient mice is limited. Thus, we aimed to compare glucose metabolic parameters, gut microbiota composition and inflammatory cytokine levels between TRIM31−/− and wild-type (WT) mice, and further investigate whether or not certain gut microbiota taxon correlates with specific metabolic parameters and inflammation cytokines in TRIM31-deficient mice. TRIM31−/− mice showed glucose intolerance and insulin resistance, with a significant difference in gut microbiota composition, characterized by increased abundance of Prevotellaceae and Veillonellaceae. TRIM31−/− mice with impaired glucose metabolism was accompanied by elevated serum tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) concentrations, as well as upregulated caecal TNF-α, IL-1β, caspase-1, and NLRP3 expressions. Furthermore, elevated p-IRS-1/IRS-1 protein expression, and decreased Akt Thr308 phosphorylation were observed in TRIM31−/− mice. Prevotellaceae abundance was positively associated with caecal IL-1β mRNA expression, and Veillonellaceae was associated with higher TNF-α mRNA expression and serum insulin concentration. In conclusion, our study is novel in showing that TRIM31 deficiency is associated with impaired glucose metabolism and disrupted gut microbiota in mice. This study contributes to the theoretical foundation on the potential relationship between TRIM31 deficiency and the development of abnormal glucose metabolism.
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