Impact of hepatocyte-specific deletion of staphylococcal nuclease and tudor domain containing 1 (SND1) on liver insulin resistance and acute liver failure of mice.
Impact of hepatocyte-specific deletion of staphylococcal nuclease and tudor domain containing 1 (SND1) on liver insulin resistance and acute liver failure of mice.
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DOI：
10.1080/21655979.2021.1974653
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发表时间：
2021-12
期刊：
影响因子：
4.9
通讯作者：
Gao X
中科院分区：
文献类型：
--
作者：
Zhao C;Cui X;Zhao Y;Qian B;Zhang N;Xin L;Ha C;Yang J;Wang X;Gao X
虽然我们以前的研究表明，改善高脂饮食（HFD）诱导的肝脏脂肪变性和胰岛素抵抗的全球SND 1转基因小鼠，参与SND 1功能丧失的肝脏代谢仍然难以捉摸。在此，我们的目的是探讨肝细胞特异性SND 1缺失对胰岛素抵抗小鼠的潜在影响。由于SND 1被报道与炎症反应有关，因此还研究了急性肝衰竭（ALF）的病理生物学特征。因此，我们首次构建了SND 1基因的条件性肝基因敲除（LKO）小鼠。在HFD条件下，肝脏SND 1的缺失影响小鼠的白色脂肪组织的重量，但不影响小鼠的大体形态、体重、胆固醇水平、肝脏重量和肝脏脂肪变性。此外，我们未能观察到HFD诱导的胰岛素抵抗或脂多糖/D-半乳糖胺诱导的（LPS/D-GaIN）ALF在LKO和野生型（WT）小鼠之间在炎症和组织损伤方面的显著差异。与阴性对照相比，基于几个基因表达综合数据集，包括GSE 23343、GSE 160646、GSE 120243、GSE 48794、GSE 13271、GSE 151268、GSE 62026、GSE 120652和GSE 38941，在具有胰岛素抵抗或ALF的各种样品中不存在差异SND 1表达。SND 1结合伴侣或相关基因的富集结果表明与RNA或脂质代谢相关的一系列问题，而不是葡萄糖稳态或肝功能衰竭。总之，肝脏SND 1不足以改变小鼠肝脏胰岛素抵抗和急性肝功能衰竭的表型。在应激过程中，各器官中的SND 1可能通过影响脂质代谢相关RNA转录物的表达来协同调节葡萄糖稳态。
Although our previous research shows an ameliorated high-fat diet (HFD)-induced hepatic steatosis and insulin resistance in global SND1 transgenic mice, the involvement of SND1 loss-of-function in hepatic metabolism remains elusive. Herein, we aim to explore the potential impact of hepatocyte-specific SND1 deletion on insulin-resistant mice. As SND1 is reported to be linked to inflammatory response, the pathobiological feature of acute liver failure (ALF) is also investigated. Hence, we construct the conditional liver knockout (LKO) mice of SND1 for the first time. Under the condition of HFD, the absence of hepatic SND1 affects the weight of white adipose tissue, but not the gross morphology, body weight, cholesterol level, liver weight, and hepatic steatosis of mice. Furthermore, we fail to observe significant differences in either HFD-induced insulin resistance or lipopolysaccharide/D-galactosamine-induced (LPS/D-GaIN) ALF between LKO and wild type (WT) mice in terms of inflammation and tissue damage. Compared with negative controls, there is no differential SND1 expression in various species of sample with insulin resistance or ALF, based on several gene expression omnibus datasets, including GSE23343, GSE160646, GSE120243, GSE48794, GSE13271, GSE151268, GSE62026, GSE120652, and GSE38941. Enrichment result of SND1-binding partners or related genes indicates a sequence of issues related to RNA or lipid metabolism, but not glucose homeostasis or hepatic failure. Overall, hepatic SND1 is insufficient to alter the phenotypes of hepatic insulin resistance and acute liver failure in mice. The SND1 in various organs is likely to cooperate in regulating glucose homeostasis by affecting the expression of lipid metabolism-related RNA transcripts during stress.
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