Mechanisms and Therapeutic Strategies for MAFLD Targeting TLR4 Signaling Pathways.

IF 4.7 3区 医学 Q2 IMMUNOLOGY Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2023-12-21 DOI:10.1159/000535524
Guanghui Ren, Changchuan Bai, Sitong Yi, Qingwei Cong, Ying Zhu
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Abstract

Background: Metabolic-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases. The underlying pathophysiological mechanisms are intricate and involve various factors. Unfortunately, there is currently a lack of available effective treatment options. Toll-like receptors (TLRs) are a group of pattern-recognition receptors that are responsible for activating the innate immune system. Research has demonstrated that TLR4 plays a pivotal role in the progression of MAFLD by facilitating the pathophysiological mechanisms.

Summary: Lipid peroxidation, pro-inflammatory factors, insulin resistance (IR), and dysbiosis of intestinal microbiota are considered as the pathogenic mechanisms of MAFLD. This review summarizes the impact of TLR4 signaling pathways on the progression of MAFLD, specifically in relation to lipid metabolic disorders, IR, oxidative stress, and gut microbiota disorders. Additionally, we emphasize the potential therapeutic approaches for MAFLD that target TLR4 signaling pathways, including the use of plant extracts, traditional Chinese medicines, probiotics, pharmaceuticals such as peroxisome proliferator-activated receptor antagonists and farnesol X agonists, and lifestyle modifications such as dietary changes and exercise also considered. Furthermore, TLR4 signaling pathways have also been linked to the lean MAFLD.

Key messages: TLR4 plays a crucial role in MAFLD by triggering IR, buildup of lipids, imbalance in gut microbiota, oxidative stress, and initiation of immune responses. The mitigation of MAFLD can be accomplished by suppressing the TLR4 signaling pathway. In the future, it could potentially emerge as a therapeutic target for the condition.

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针对 TLR4 信号通路的 MAFLD 机制和治疗策略。
背景:代谢相关性脂肪肝(MAFLD)是最常见的慢性肝病之一:代谢相关性脂肪肝(MAFLD)是最常见的慢性肝病之一。其潜在的病理生理机制错综复杂,涉及多种因素。遗憾的是,目前缺乏有效的治疗方案。Toll 样受体(TLRs)是一组模式识别受体,负责激活先天性免疫系统。摘要:脂质过氧化、促炎、胰岛素抵抗(IR)和肠道微生物群失调被认为是 MAFLD 的致病机制。本综述总结了TLR4信号通路对MAFLD进展的影响,特别是与脂质代谢紊乱、IR、氧化应激和肠道微生物群紊乱的关系。此外,我们还强调了针对 TLR4 信号通路的 MAFLD 潜在治疗方法,包括使用植物提取物、传统中药、益生菌、PPAR 拮抗剂和 FXR 激动剂等药物,以及改变饮食和运动等生活方式。此外,TLR4 信号通路也与 MAFLD 瘦人症有关:TLR4通过引发胰岛素抵抗、脂质堆积、肠道微生物群失衡、氧化应激和免疫反应的启动,在MAFLD中发挥着至关重要的作用。可以通过抑制 TLR4 信号通路来缓解 MAFLD。未来,它有可能成为该疾病的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Innate Immunity
Journal of Innate Immunity 医学-免疫学
CiteScore
10.50
自引率
1.90%
发文量
35
审稿时长
7.5 months
期刊介绍: The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.
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