Val-Val-Tyr-Pro 通过调节肠道微生物群和肠肝轴激活来预防小鼠非酒精性脂肪性肝炎,Journal of Cellular and Molecular Medicine

当前位置： X-MOL 学术 › J. Cell. Mol. Med. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Val-Val-Tyr-Pro 通过调节肠道微生物群和肠肝轴激活来预防小鼠非酒精性脂肪性肝炎
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2021-01-05 , DOI: 10.1111/jcmm.16229
Xinshu Xie ₁ , Lang Zhang ₂ , Shun Yuan ₁ , Huilan Li ₁ , Chaojun Zheng ₁ , Saisai Xie ₁ , Yongbing Sun ₁ , Changhua Zhang ₁ , Rikang Wang _{1,

3} , Yi Jin ₁

Affiliation

Val-Val-Tyr-Pro (VVYP) 肽是珠蛋白消化物 (GD) 的主要活性成分之一。我们之前的研究表明，VVYP 可以预防对乙酰氨基酚和四氯化碳引起的小鼠急性肝功能衰竭并降低血脂水平。然而，尚未发现 VVYP 在治疗非酒精性脂肪性肝炎 (NASH) 中的作用和潜在机制。我们目前的研究旨在调查 VVYP 对 NASH 的预防作用及其潜在的具体机制。我们发现 VVYP 抑制了暴露于游离脂肪酸 (FFA) 混合物的 L-02 细胞的细胞毒性和脂质积累。VVYP有效减轻蛋氨酸-胆碱缺乏（MCD）饮食引起的肝损伤，通过降低血清丙氨酸氨基转移酶（ALT）/天冬氨酸氨基转移酶（AST）/甘油三酯（TG）/非酯化脂肪酸（NEFA）的水平和改善肝脏组织学来证明。VVYP降低了MCD饮食喂养的小鼠肝脏中脂质合成相关基因的表达水平和促炎细胞因子的水平。此外，VVYP 抑制 LPS 水平的升高并逆转 MCD 饮食诱导的肝线粒体功能障碍。同时，VVYP 显着增加了有益细菌的丰度，例如 VVYP抑制LPS水平升高并逆转MCD饮食诱导的肝线粒体功能障碍。同时，VVYP 显着增加了有益细菌的丰度，例如 VVYP抑制LPS水平升高并逆转MCD饮食诱导的肝线粒体功能障碍。同时，VVYP 显着增加了有益细菌的丰度，例如在高脂肪饮食 (HFD) 喂养的小鼠中，真细菌科、coriobacteriacease、Desulfovibrionaceae、S24-7和Bacteroidia，然而，VVYP 降低了乳杆菌的丰度。此外，VVYP通过促进粘蛋白和紧密连接（TJ）相关基因的表达并抑制随后的肝脏炎症反应，赋予肠道屏障保护作用。这些结果表明 VVYP 对 NASH 的保护作用是通过调节肠道微生物群失衡和相关的肠-肝轴激活介导的。VVYP 可能是一种很有前途的 NASH 候选药物。

"点击查看英文标题和摘要"

Val‐Val‐Tyr‐Pro protects against non‐alcoholic steatohepatitis in mice by modulating the gut microbiota and gut‐liver axis activation

Val‐Val‐Tyr‐Pro (VVYP) peptide is one of the main active components of Globin digest (GD). Our previous studies indicated that VVYP could protect against acetaminophen and carbon tetrachloride‐induced acute liver failure in mice and decrease blood lipid level. However, the effects and underlying mechanisms of VVYP in the treatment of non‐alcoholic steatohepatitis (NASH) have not been discovered. Our present study was designed to investigate the preventive effect of VVYP on NASH and its underlying specific mechanisms. We found that VVYP inhibited the cytotoxicity and lipid accumulation in L‐02 cells that were exposed to a mixture of free fatty acid (FFA). VVYP effectively alleviated the liver injury induced by methionine‐choline‐deficient (MCD) diet, demonstrated by reducing the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/triglycerides (TG)/non‐esterified fatty acids (NEFA) and improving liver histology. VVYP decreased expression levels of lipid synthesis‐related genes and reduced levels of the proinflammation cytokines in the liver of mice fed by MCD diet. Moreover, VVYP inhibited the increased level of LPS and reversed the liver mitochondria dysfunction induced by MCD diet. Meanwhile, VVYP significantly increased the abundance of beneficial bacteria such as Eubacteriaceae, coriobacteriacease, Desulfovibrionaceae, S24‐7 and Bacteroidia in high‐fat diet (HFD)‐fed mice, however, VVYP reduced the abundance of Lactobacillus. Moreover, VVYP conferred the protective effect of intestinal barrier via promoting the expression of the mucins and tight junction (TJ)‐associated genes and inhibited subsequent liver inflammatory responses. These results indicated that the protective role of VVYP on NASH is mediated by modulating gut microbiota imbalance and related gut‐liver axis activation. VVYP might be a promising drug candidate for NASH.

更新日期：2021-02-11

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>