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提取物通过增强高脂肪饮食诱导的脂肪肝小鼠模型中的胆汁酸合成来预防肝脂肪变性。

Extract Prevents Hepatic Steatosis by Enhancing Bile Acid Synthesis in a High-Fat Diet-Induced Fatty Liver Mouse Model.

机构信息

Digital Omics Research Center, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.

Critical Diseases Diagnostics Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.

出版信息

Nutrients. 2024 Mar 20;16(6):893. doi: 10.3390/nu16060893.

DOI:10.3390/nu16060893
PMID:38542804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10975839/
Abstract

We aimed to identify the mechanism underlying the preventive effects of non-alcoholic fatty liver disease (NAFLD) through consumption using liver proteomic and bioinformatic analysis. C57BL/6J mice were categorized into three groups: those receiving a standard chow diet (NCD), those on a high-fat diet (HFD), and those on an HFD supplemented with 5% extract (PRE). After a 12-week period, PRE-fed mice exhibited a noteworthy prevention of hepatic steatosis. Protein identification and quantification in liver samples were conducted using LC-MS/MS. The identified proteins were analyzed through Ingenuity Pathway Analysis software, revealing a decrease in proteins associated with FXR/RXR activation and a concurrent increase in cholesterol biosynthesis proteins in the PRE-treated mouse liver. Subsequent network analysis predicted enhanced bile acid synthesis from these proteins. Indeed, the quantity of bile acids, which was reduced in HFD conditions, increased in the PRE group, accompanied by an elevation in the expression of synthesis-related proteins. Our findings suggest that the beneficial effects of PRE in preventing hepatic steatosis may be mediated, at least in part, through the modulation of FXR/RXR activation, cholesterol biosynthesis, and bile acid synthesis pathways.

摘要

我们旨在通过肝脏蛋白质组学和生物信息学分析来确定非酒精性脂肪性肝病 (NAFLD) 通过 消耗的预防作用的机制。将 C57BL/6J 小鼠分为三组:接受标准饲料饮食(NCD)的组、高脂肪饮食(HFD)的组和补充 5%提取物(PRE)的 HFD 的组。经过 12 周后,PRE 喂养的小鼠显著预防了肝脂肪变性。使用 LC-MS/MS 对肝样品中的蛋白质进行鉴定和定量。通过 Ingenuity Pathway Analysis 软件分析鉴定的蛋白质,表明与 FXR/RXR 激活相关的蛋白质减少,同时 PRE 处理的小鼠肝中胆固醇生物合成蛋白增加。随后的网络分析预测这些蛋白质的胆汁酸合成增强。事实上,在 HFD 条件下减少的胆汁酸的量在 PRE 组中增加,同时与合成相关的蛋白质的表达升高。我们的研究结果表明,PRE 预防肝脂肪变性的有益作用可能至少部分通过调节 FXR/RXR 激活、胆固醇生物合成和胆汁酸合成途径来介导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2b8/10975839/aa67a07a3078/nutrients-16-00893-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2b8/10975839/3a526676e944/nutrients-16-00893-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2b8/10975839/eed9639d836e/nutrients-16-00893-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2b8/10975839/f4bebd8b2329/nutrients-16-00893-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2b8/10975839/aa67a07a3078/nutrients-16-00893-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2b8/10975839/3a526676e944/nutrients-16-00893-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2b8/10975839/eed9639d836e/nutrients-16-00893-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2b8/10975839/f4bebd8b2329/nutrients-16-00893-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2b8/10975839/aa67a07a3078/nutrients-16-00893-g004.jpg

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FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption.FXR 激活通过依赖于胆汁酸的脂质吸收减少来预防 NAFLD。
Cell Metab. 2021 Aug 3;33(8):1671-1684.e4. doi: 10.1016/j.cmet.2021.06.012. Epub 2021 Jul 15.
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Natural products and analogs as preventive agents for metabolic syndrome via peroxisome proliferator-activated receptors: An overview.
天然产物和类似物作为过氧化物酶体增殖物激活受体的代谢综合征预防剂:概述。
Eur J Med Chem. 2021 Oct 5;221:113535. doi: 10.1016/j.ejmech.2021.113535. Epub 2021 May 10.
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Combined ASBT Inhibitor and FGF15 Treatment Improves Therapeutic Efficacy in Experimental Nonalcoholic Steatohepatitis.联合 ASBT 抑制剂和 FGF15 治疗可改善实验性非酒精性脂肪性肝炎的治疗效果。
Cell Mol Gastroenterol Hepatol. 2021;12(3):1001-1019. doi: 10.1016/j.jcmgh.2021.04.013. Epub 2021 May 7.
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