Knockdown of RASD1 improves MASLD progression by inhibiting the PI3K/AKT/mTOR pathway.

IF 3.9 2区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Lipids in Health and Disease Pub Date : 2024-12-27 DOI:10.1186/s12944-024-02419-z

Guifang Zeng, Xialei Liu, Zhouying Zheng, Jiali Zhao, Wenfeng Zhuo, Zirui Bai, En Lin, Shanglin Cai, Chaonong Cai, Peiping Li, Baojia Zou, Jian Li

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引用次数: 0

Abstract

Background: There is still no reliable therapeutic targets and effective pharmacotherapy for metabolic dysfunction-associated steatotic liver disease (MASLD). RASD1 is short for Ras-related dexamethasone-induced 1, a pivotal factor in various metabolism processes of Human. However, the role of RASD1 remains poorly illustrated in MASLD. Therefore, we designed a study to elucidate how RASD1 could impact on MASLD as well as the mechanisms involved.

Methods: The expression level of RASD1 was validated in MASLD. Lipid metabolism and its underlying mechanism were investigated in hepatocytes and mice with either overexpression or knockdown of RASD1.

Results: Hepatic RASD1 expression was upregulated in MASLD. Lipid deposition was significantly reduced in RASD1-knockdown hepatocytes and mice, accompanied by a marked downregulation of key genes in the signaling pathway of de novo lipogenesis. Conversely, RASD1 overexpression in hepatocytes had the opposite effect. Mechanistically, RASD1 regulated lipid metabolism in MASLD through the PI3K/AKT/mTOR signaling pathway.

Conclusions: We discovered a novel role of RASD1 in MASLD by regulating lipogenesis via the PI3K/AKT/mTOR pathway, thereby identifying a potential treatment target for MASLD.

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敲低RASD1可通过抑制PI3K/AKT/mTOR通路改善MASLD的进展。

背景：代谢功能障碍相关脂肪变性肝病（MASLD）目前仍没有可靠的治疗靶点和有效的药物治疗方法。RASD1是ras相关地塞米松诱导1 （Ras-related dexamethasone-induced 1）的简称，是人类多种代谢过程中的关键因子。然而，RASD1在MASLD中的作用仍然知之甚少。因此，我们设计了一项研究来阐明RASD1如何影响MASLD以及所涉及的机制。方法：检测MASLD中RASD1的表达水平。研究了RASD1过表达或低表达的肝细胞和小鼠的脂质代谢及其潜在机制。结果：MASLD患者肝脏RASD1表达上调。在rasd1敲除的肝细胞和小鼠中，脂质沉积显著减少，并伴有新生脂肪生成信号通路中关键基因的显著下调。相反，肝细胞中RASD1过表达具有相反的效果。机制上，RASD1通过PI3K/AKT/mTOR信号通路调节MASLD的脂质代谢。结论：我们发现了RASD1通过PI3K/AKT/mTOR通路调节脂肪生成在MASLD中的新作用，从而确定了MASLD的潜在治疗靶点。

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

Lipids in Health and Disease 生物-生化与分子生物学

CiteScore

7.70

自引率

2.20%

发文量

122

审稿时长

3-8 weeks

期刊介绍： Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds. Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.

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