抑制neuropilin-1可改善高脂饮食诱导的肥胖小鼠的非酒精性脂肪性肝病。

IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM
Jian Zhou, Sian Xu, Yue Zhu, Xin Li, Ao Wang, Junfang Hu, Li Li, Yan Liu
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引用次数: 0

摘要

背景:研究发现,neuropilin-1在脂质代谢和肥胖相关的胰岛素抵抗中起关键作用;在此基础上,本研究旨在探讨抑制neuropilin-1对高脂饮食(high-fat-diet, HFD)诱导的肥胖小鼠非酒精性脂肪肝(non-alcoholic fatty liver, NAFLD)疾病的影响及其作用机制。方法:首先,成功构建含有NRP1基因的pcDNA3.1-NRP-1重组质粒和NRP1 RNA干扰质粒shRNA-NRP1。将36只C57BL/6小鼠随机分为6组:空白组、对照组、pcDNA3.1注射组、pcDNA3.1- nrp -1注射组、pGenesil-1.1注射组和shRNA-NRP1注射组。测定小鼠肝脏中phospho-PI3K、phospho-AKT、phospho-mTOR和neuropilin-1的表达,以及体重、肝重、血糖、血清转氨酶和血脂水平。结果:注射pcdna3.1 - nrp1后HFD喂养小鼠的体重和肝脏质量明显高于对照组,而注射shRNA-NRP1后HFD喂养小鼠的体重和肝脏质量明显降低。结果还显示,neuropilin-1的表达可显著影响HFD喂养小鼠肝脏脂肪变性的严重程度,降低血清FPG、LDL、AST、ALT水平以及肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)和IL-6 mRNA的表达。此外,Neuropilin-1的表达也会影响小鼠的p-PI3K、p-AKT和p-mTOR。结论:本研究表明,抑制neuropilin-1可通过调节PI3K/AKT/mTOR信号通路,通过降低肥胖小鼠的体重和减轻炎症来改善NAFLD疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibition of neuropilin-1 improves non-alcoholic fatty liver disease in high-fat-diet induced obese mouse.

Background: Research findings indicate that neuropilin-1 plays a critical role in lipid metabolism and obesity-associated insulin resistance; on such a basis, the aim of this study was to explore the effects and working mechanism of neuropilin-1 inhibition on the non-alcoholic fatty liver (NAFLD) disease in high-fat-diet (HFD) induced obese mice.

Methods: Firstly, the pcDNA3.1-NRP-1 recombinant plasmid containing neuropilin-1 (NRP1) gene and NRP1 RNA interference plasmid shRNA-NRP1 were successfully constructed. A total of 36 C57BL/6 mice were randomly assigned to 6 groups, blank group, control group, pcDNA3.1 injection group, pcDNA3.1-NRP-1 injection group, pGenesil-1.1 injection group and shRNA-NRP1 injection group. Expression of phospho-PI3K, phospho-AKT, phospho-mTOR and neuropilin-1 in liver was measured as well as body and liver weight, blood glucose, serum transaminases and lipid levels of the mice.

Results: The weight and liver mass of HFD fed mice injected with pcDNA3.1-NRP-1 were significantly higher than those from the control group, but their body weight and liver mass decreased significantly after shRNA-NRP1 injection. The results also showed that neuropilin-1 expression can significantly influence the severity of hepatic steatosis in HFD fed mice, decreased serum FPG, LDL, AST, ALT levels and the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 mRNA. In addition, the Neuropilin-1 expression will also influence the p-PI3K, p-AKT and p-mTOR in mice.

Conclusions: This study concluded that the inhibition of neuropilin-1 could improve NAFLD disease by decreasing body weight and reduce inflammation in HFD induced obese mice by modulating the PI3K/AKT/mTOR signaling pathway.

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